Intraductal Papillary Mucinous Neoplasms and the Risk of Diabetes Mellitus in Patients Undergoing Resection Versus Observation.

OBJECTIVE: The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation. METHODS: Patients diagnosed with IPMN were identified from institutional databases, divided into two groups based on treatment type, pancreatectomy versus clinical observation, and subsequently evaluated. Standard demographic and clinicopathologic variables, fasting glucose, diabetic status, and pancreatic volume data, were obtained and compared between groups. RESULTS: One hundred thirty-four IPMN patients were identified; 103 (77 %) underwent pancreatectomy and 31 (23 %) were observed. Baseline DM rate was 18 % (24/134). This was not different between groups [17 % (17/103) resected vs. 23 % (7/31) observed, p = 0.51]. Median follow-up was 53 months and new/progressive DM occurred in 37 (28 %) patients with no difference between groups [29 (28 %) resected vs. 8 (26 %) observed, p = 0.74]. Among resected patients, degree of dysplasia was associated with increase risk of new/progressive DM [moderate dysplasia OR 5.76 (1.24-26.79) and severe dysplasia OR 9.43 (1.54-57.74), p = 0.04], while procedure type and remnant volume were not. CONCLUSIONS: The incidence and prevalence of DM among patients with IPMN was high and did not differ between resected and observed groups. Degree of dysplasia, not the amount of resected pancreas, was associated with increased risk of DM, suggesting that the presence or development of DM may be a marker of malignant progression. Confirmatory studies are required.

Prevalence of diabetes mellitus in patients with newly evaluated papillary thyroid cancer.

BACKGROUND: This study investigates whether diabetes mellitus is a risk factor for the development of papillary thyroid cancer, using an age-, gender-, and race-matched analysis. METHODS: We retrospectively reviewed the charts of 1559 patients with newly evaluated thyroid cancer over a 4-year period at our institution and identified 1313 patients (84%) with papillary thyroid carcinoma. Characteristics of patients with diabetes versus those without diabetes were compared with a chi-square test for categorical variables and the Wilcoxon Rank Sum test for numeric variables. The prevalence of diabetes among patients with papillary thyroid carcinoma at our institution was compared (using an age-, gender-, and race-matched analysis) with that expected based on data from the continuous National Health and Nutrition Examination Survey (NHANES) from the same time period. RESULTS: For patients with papillary thyroid carcinoma, the median age was 47 years; 74% were female; 83% were white; and the prevalence of diabetes was 8%. Among those with diabetes, 92% had type 2 diabetes, and 24% were treated with insulin. Risk factors for diabetes included age and race. The prevalence of diabetes among patients with papillary thyroid carcinoma of all ages versus that among patients from NHANES of all ages was not significantly different (RR 1.07, CI 0.88 - 1.28). The prevalence of diabetes among patients with papillary thyroid cancer who were 44 years of age or younger versus that among patients from NHANES who were 44 years of age or younger, however, was significantly increased (RR 2.32, CI 1.37 - 3.66). There was no significant difference when subgroup analysis was performed by gender or race. CONCLUSIONS: We found an increased prevalence of diabetes in patients with papillary thyroid carcinoma who were 44 years of age or younger.

Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes.

OBJECTIVE: This study evaluated the glycosylated hemoglobin (HbA(1c)-lowering effect of colesevelam hydrochloride, a bile acid sequestrant, in subjects with type 2 diabetes that was inadequately controlled by existing antihyperglycemic therapy. METHODS: After a 4-week placebo run-in period, subjects with type 2 diabetes and an HbA(1c) value of 7.0% to 10.0% were randomized to receive colesevelam 3.75 g/d or matching placebo for 12 weeks. Subjects' previous oral anti hyperglycemic medication (sulfonylurea and/or metformin) was continued throughout the study. Fasting blood samples were obtained at weeks -5, -1, 0, 1, 4, 8, and 12. The primary efficacy end point was the change in HbA(1c) from baseline to week 12. Secondary end points included changes in fructosamine levels, fasting plasma glucose levels, postprandial glucose level, and meal glucose response (ie, difference between preprandial and postprandial levels), and percent changes in lipid parameters from baseline to week 12. RESULTS: The 65 randomized subjects (31 colesevelam, 34 placebo) had a mean age of 56.2 years and a mean body mass index of 32.4 kg/m(2); 55.4% were male and 53.8% were white. The difference in least squares (LS) mean (SE) change in HbA(1c) between the colesevelam group and the placebo group was -0.5% (0.18) (P = 0.007). In subjects with a baseline HbAIc > or = 8.0%, the difference in LS mean change in HbA(1c) was -1.0% (0.27) (P = 0.002). Relative to placebo, colesevelam treatment was associated with reductions in levels of fructosamine (-29.0 [10.9] pmol/L; P = 0.011) and postprandial glucose (-31.5 [13.6] mg/dL; P = 0.026). The mean percent change in low-density lipoprotein cholesterol was -9.6% in the colesevelam group, compared with 2.1% in the placebo group (treatment difference, -11.7% [4.2]; P = 0.007); the respective mean percent changes in total cholesterol were -4.0% and 3.4% (treatment difference, -7.3% [3.0]; P = 0.019). Colesevelam also was associated with significant decreases in the percent change in apolipoprotein B (P = 0.003) and low-density lipoprotein particle concentration (P = 0.037). The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups, although treatment-related adverse events were more frequent in the colesevelam group than in the placebo group (29.0% vs 8.8%, respectively). The most frequent TEAEs in the colesevelam group were gastrointestinal disorders (22.6%), primarily constipation (19.4%), compared with an 8.8% incidence of gastrointestinal disorders (0% constipation) in the placebo group. There were no significant changes in body weight or the occurrence of hypoglycemia between treatment groups. CONCLUSIONS: In these subjects with type 2 diabetes, 12 weeks of colesevelam treatment were associated with significant reductions in HbA(1c) and in fructosamine and postprandial glucose levels compared with placebo. The 2 groups had a similar adverse-event profile, with the exception of an increased incidence of constipation in the colesevelam group. These results suggest that colesevelam may improve both lipid control and glycemic control in patients with type 2 diabetes receiving oral antihyperglycemic medications.

A review of combination regimens for osteoporosis--prevention and treatment.

Two long-used interventions for reducing the morbidity and mortality associated with osteoporosis are postmenopausal hormone replacement therapy (HRT) and treatment with antiresorptive agents. Postmenopausal HRT works through prevention of osteoporosis, whereas antiresorptive agents, such as the bisphosphonates, reverse low bone mass. Because of their different mechanisms, it has been thought that combining the two therapies would yield additive improvements in bone mineral density (BMD) and in fracture risk reduction. Results from several recent clinical trials in postmenopausal women with low bone mass support this idea, demonstrating clinically relevant additive improvements in BMD after treatment with HRT (or a selective estrogen receptor modulator) plus a bisphosphonate. Data regarding fracture rates after HRT and bisphosphonate combination therapy are unavailable, however. A newer osteoporosis treatment is subcutaneously injected parathyroid hormone (PTH). Treatment with PTH stimulates new bone formation, and recent studies have shown that PTH monotherapy reduces fracture rates. Initial data from studies of HRT and PTH combination therapy have shown impressive gains in BMD, but fracture rate data have not been published. Use of HRT for osteoporosis, either alone or in combination with a bisphosphonate or PTH, has become problematic since the recent report of a small number of serious adverse effects associated with HRT in the Women's Health Initiative.