Total Pancreatectomy with Percutaneous Islet Autotransplant after Remote Islet Processing: A Viable Paradigm?

OBJECTIVES: Total pancreatectomy with islet autotransplant (TPIAT) is important therapy for select chronic pancreatitis (CP) patients. The specialized technique of islet isolation limits widespread TPIAT use. We hypothesized that remote islet isolation provides satisfactory islet yield and perioperative outcomes. METHODS: Retrospective review of TPIAT patients between 2020 and 2022. Islet isolation was performed off-site, with percutaneous intraportal islet autotransplant (IAT) completed the morning following pancreatectomy. Demographics and perioperative outcomes were analyzed. RESULTS: Fourteen patients underwent TPIAT; median age was 43 [interquartile range 12.5] years. Operation occurred 7.5 [14.8] years after pancreatitis diagnosis. The most common pancreatitis etiology was genetic (50%). All patients underwent preoperative endoscopic therapy; three underwent prior pancreatectomy. Operative time was 236 [51] minutes; subsequent percutaneous IAT time was 87 [35] minutes. The islet equivalent (IEQ)/kilogram (kg) yield was 3,456 [3,815] IEQ/kg. Nine patients had positive islet cultures. Two thromboembolic events and one bacteremia occurred. One perihepatic hematoma occurred after percutaneous portal venous access. Median postoperative length of stay was 14.5 days, and five patients (36%) were readmitted within 90 days. All patients were discharged home on insulin. No mortality occurred. CONCLUSION: Total pancreatectomy with remote islet isolation provides excellent islet yield for autotransplant and satisfactory perioperative outcomes.

The Diabetes Tune-Up Group: A Multidisciplinary Approach to Improve Diabetes Distress and A1C Among Adults With Type 1 and Type 2 Diabetes.

PURPOSE: The purpose of this study was to assess the feasibility of delivering the Diabetes Tune-Up Group (DTU), a cognitive-behavioral-therapy-based (CBT) multidisciplinary intervention for adults with diabetes distress and elevated A1C using a group in-person delivery format. METHODS: The DTU intervention consisted of 6 weekly group sessions (90 minutes in duration per session). The groups were cofacilitated by a diabetes care and education specialist (DCES) and a master's-level clinical psychology trainee. The intervention integrated CBT with patient-centered diabetes education. Using a pre/post study design, participants completed assessments at baseline, post-intervention, and 3 months following the intervention. RESULTS: The sample consisted of 29 adults with type 1 diabetes (N = 8) or type 2 diabetes (N = 21) who were predominantly female (79%), White (59%), and educated (56% with a college degree or greater). Participants attended 131 total sessions out of 174 possible sessions, for an overall attendance rate of 75.3%. At 3-month follow-up, significant improvements were observed in A1C values (mean decrease = 0.39%). Diabetes distress improved significantly from baseline (mean = 3.44, SD = 0.68) to post-intervention (mean = 2.94, SD = 0.68), and 3-month follow-up (mean = 2.55, SD = 0.75). Significant improvements were also observed in diabetes self-efficacy from baseline to post-intervention and at 3-month follow-up. CONCLUSIONS: This group-based, multidisciplinary intervention resulted in improvements in A1C, diabetes distress, and patient self-efficacy in caring for diabetes. Future studies to validate this intervention approach across settings and delivery platforms are needed.

Use of Continuous Etomidate Infusion to Rapidly Correct Hypercortisolism in a Patient With Disseminated Nocardiosis.

Cushing's syndrome (CS) is an immunocompromised state characterized by impaired cellular and adaptive immunity due to hypercortisolism. This imbalance in the immune system leads to a high risk of opportunistic infections which can potentially prove fatal. In such patients, mortality can be reduced with early diagnosis and effective management of the underlying hypercortisolism. In this case report, we describe how prompt reduction of cortisol levels using a low dose continuous etomidate infusion was pivotal in effective treatment of an opportunistic infection, disseminated nocardiosis, in a 29-year-old female with Cushing's syndrome. We also discuss how treatment with antibiotics including empiric therapy with Imipenem and sulfamethoxazole/trimethoprim (SMX/TMP) and definite therapy as per susceptibility testing, with amikacin, SMX/TMP, and doxycycline helped to prevent adverse outcomes. Through this case, we aim to emphasize that infiltrates or cavitary lesions on the computed tomography (CT) scan of the chest in a patient with Cushing's syndrome should raise concern for nocardiosis, and prompt management with antibiotics should be initiated. Similarly, disseminated nocardiosis should always raise concern for possible immune deficiency states like Cushing's syndrome. Our case is unique in detailing the significance of using etomidate to acutely lower cortisol levels in a patient with endogenous CS and widespread invasive opportunistic infection. The pharmacology aspects of the Etomidate, in this case, have been published in the Journal of Pharmacy Practice and cited appropriately in this article.

Pituitary macroadenoma in a patient with POEMS syndrome in conjunction with Castleman disease: first report of a case and review of related literature.

OBJECTIVE: To describe the first reported case of a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) in conjunction with the endocrinologic manifestation of panhypopituitarism due to a large clinically nonfunctioning pituitary adenoma. METHODS: We present the clinical, laboratory, and radiologic details of the case and review the relevant updated literature. RESULTS: A 48-year-old man with hypopituitarism and progressive polyneuropathy presented to an outside hospital with confusion and diaphoresis. He also had diffuse lymphadenopathy, monoclonal gammopathy, and skin lesions consistent with a diagnosis of POEMS syndrome. Cytopathologic study of a lymph node showed findings consistent with Castleman disease. A large suprasellar mass was found to be the cause of the hypopituitarism. CONCLUSION: POEMS syndrome is a rare paraneoplastic condition, commonly associated with Castleman disease, that manifests with progressive distal polyneuropathy and a monoclonal plasma cell disorder, often accompanied by endocrinopathy, organomegaly, skin changes, sclerotic bone lesions, ascites, erythrocytosis, and thrombocytosis. Our current patient had all 5 classic features of POEMS syndrome along with some diagnostic elements of Castleman disease, sclerotic bone lesions, and thrombocytosis. To our knowledge, this is the first known reported case of a patient whose endocrinologic manifestation of POEMS syndrome was panhypopituitarism attributable to a large clinically nonfunctioning pituitary adenoma.

Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting.

BACKGROUND: Exenatide is an antidiabctic agent currently indicated as adjunctive therapy with oral agents for the treatment of type 2 diabetes mellitus (T2DM). Limited published data exist on the off-label use of exenatide in conjunction with insulin in the treatment of T2DM. OBJECTIVE: The aim of this retrospective study was to examine the effects of exenatide on glycemic control, weight, and insulin dose in patients with T2DM treated with insulin. METHODS: Patients with T2DM receivirg insulin and adjuvant therapy with exenatide at an endocrinology clinic at a university hospital for up to 27 months were eligible for inclusion. Glycosylated hemoglobin (HbA(1c)), weight, insulin doses (total, prandial, and basal), concurrent oral antidiabetic medications, and adverse events were ascertained by retrospective review of medical records and were considered the clinical parameters of interest. The last observation in 4 specified time intervals (0-6, 6-12, 12-18, and 18-27 months) for each clinical parameter was used in the analysis. RESULTS: Of the 3397 patients with a confirmed diagnosis of T2DM who were seen at the clinic during the study period, 268 patients met inclusion criteria and were enrolled in the study. Of the 268 patients enrolled, 38 discontinued therapy within the first 2 months, 30 were lost to follow-up, and 12 did not have evaluable data. These latter patients without sufficient data (n = 42) were not included in the primary analysis but were included in the adverse events analysis. Overall, data from 188 patients (mean [SD] age, 56 (9) years; 85 [45%] men; body mass index, 40.4 [8.4] kg/m(2); 160 [85%] white) were evaluated (mean duration of treatment, 350 [208] days) and included in all analyses. The mean baseline values for HbA(1c), weight, and total daily insulin dose before exenatide therapy were 8.05% (1.47%), 117.8 (24.7) kg, and 99.9 (90.0) U, respectively. For the 4 time intervals, the mean changes in HbA(1c) were: -0.66% (1.54%) at 0 to 6 months (P < 0.001); -0.55% (1.4%) at 6 to 12 months (P < 0.001); -0.54% (1.83%) at 12 to 18 months (P = 0.019); and -0.54% (1.37%) at 18 to 27 months (P = 0.020). Mean weight significantly declined with increasing treatment duration. Mean changes in weight were: -2.4 (5.1) kg at 0 to 6 months (P < 0.001); -4.3 (7.2) kg at 6 to 12 months (P < 0.001); -6.2 (9.7) kg at 12 to 18 months (P < 0.001); and -5.5 (10.8) kg at 18 to 27 months (P < 0.01). After 18 months, an increase in weight was observed; but the increase remained lower than baseline. The mean insulin total daily dose (TDD) was decreased in all patients at the 0- to 6-month (-18.0 [49.9] U; P < 0.001) and the 6- to 12-month (-14.8 [35.3] U; P < 0.001) intervals. Mean changes in insulin TDD during the 12- to 18-month and 18- to 27-month intervals were not statistically significant. The mean percent change from baseline in the basal insulin dose at 0 to 6 months, 6 to 12 months, 12 to 18 months, and 18 to 27 months was not statistically significant. For the 4 intervals, the mean percent change from baseline in the prandial insulin dose was -33.5% (56.2%) at 0 to 6 months (P < 0.001); -25.9% (59.7%) at 6 to 12 months (P = 0.002); -29.7% (74.8%) at 12 to 18 months (P = 0.02); and -55.7% (56.8%) at 18 to 27 months (P = 0.005). Of the 226 patients who were treated with exenatide + insulin for any length of time (including within the first 2 months), 59 (26.1%) discontinued exenatide because of adverse events. The adverse events were largely considered mild and included nausea (n = 51 [22.6% of patients]), vomiting (22 [9.7%]), hypoglycemia (9 [4.0%]), heartburn (2 [0.9%]), diarrhea (1 [0.4%]), constipation (1 [0.4%]), malaise (1 [0.4%]), and generalized edema (1 [0.4%]). Two serious adverse events occurred during the study period: acute renal failure not attributed to exenatide (1 [0.4%]); and pancreatitis (1 [0.4%]), both of which required hospitalization 1 month after the start of exenatide therapy. CONCLUSION: In this retrospective review of patients with T2DM treated in an outpatient setting, the addition of exenatide to insulin-based therapy was associated with reductions in mean HbA(1c), weight, and prandial insulin requirements for treatment periods of up to 27 months, and in total insulin requirements for treatment periods of up to 12 months.

Insulin secretion in type 1 diabetes.

Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.

Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome.

Deterioration in glucose tolerance occurs rapidly in women with polycystic ovary syndrone (PCOS), suggesting that pancreatic beta-cell dysfunction may supervene early. To determine whether the compensatory insulin secretory response to an increase in insulin resistance induced by the glucocorticoid dexamethasone differs in women with PCOS and control subjects, we studied 10 PCOS and 6 control subjects with normal glucose tolerance. An oral glucose tolerance test (OGTT) and a graded glucose infusion protocol were performed at baseline and after subjects took 2.0 mg of dexamethasone orally. Basal (Phi(b)), static (Phi(s)), dynamic (Phi(d)), and global (Phi) indexes of beta-cell sensitivity to glucose were derived. Insulin sensitivity (S(i)) was calculated using the minimal model; a disposition index (DI) was calculated as the product of S(i) and Phi. PCOS and control subjects had nearly identical fasting and 2-h glucose levels at baseline. Phi(b) was higher, although not significantly so, in the PCOS subjects. The Phi(d), Phi(s), and Phi indexes were 28, 19, and 20% higher, respectively, in PCOS subjects. The DI was significantly lower in PCOS (30.01 +/- 5.33 vs. 59.24 +/- 7.59) at baseline. After dexamethasone, control subjects averaged a 9% increase (to 131 +/- 12 mg/dl) in 2-h glucose levels; women with PCOS had a significantly greater 26% increase to 155 +/- 6 mg/dl. The C-peptide-to-glucose ratios on OGTT increased by 44% in control subjects and by only 15% in PCOS subjects. The accelerated deterioration in glucose tolerance in PCOS may result, in part, from a relative attenuation in the response of the beta-cell to the demand placed on it by factors exacerbating insulin resistance.