Mountain Diabetes and Endocrine Center

Hendersonville, NC, United States

Mountain Diabetes and Endocrine Center

Hendersonville, NC, United States
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Lane W.,Mountain Diabetes and Endocrine Center | Bailey T.S.,AMCR Institute Inc. | Gerety G.,Albany Medical College | Gumprecht J.,University of Silesia | And 5 more authors.
JAMA - Journal of the American Medical Association | Year: 2017

IMPORTANCE Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death. OBJECTIVE To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period. INTERVENTIONS Patientswere randomized 1:1 to receive once-daily insulin degludec followed by insulin glargineU100(n = 249)or toreceive insulin glargineU100followedby insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence. MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of overall severe or blood glucose-confirmed (<56mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95%CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted. RESULTS Of the 501 patients randomized (mean age, 45.9 years; 53.7%men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years' exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95%CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, -130.31 episodes per 100 PYE; 95%CI, -193.5 to -67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95%CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, -61.94 episodes per 100 PYE; 95%CI, -83.85 to -40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95%CI, 7.3%-13.3%vs 17.1%, 95%CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, -6.8%; 95%CI, -10.8%to -2.7%). CONCLUSIONS AND RELEVANCE Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks' treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes. © 2017 American Medical Association. All rights reserved.


Lane W.S.,Mountain Diabetes and Endocrine Center | Weinrib S.L.,Mountain Diabetes and Endocrine Center | Rappaport J.M.,Mountain Diabetes and Endocrine Center | Przestrzelski T.,Mountain Diabetes and Endocrine Center
Endocrine Practice | Year: 2010

Objective: To test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance. Methods: In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A 1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A 1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod. Results: Twenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m 2; mean insulin requirement, 1.7 U/kg per day; and mean hemoglobin A 1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A 1c by 1.23% (P<.001) and significantly increased the percentage of time spent in the blood glucose target range (70-180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P<.001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion. Conclusions: U500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population. Copyright © 2010 AACE.


Lane W.S.,Mountain Diabetes and Endocrine Center | Weinrib S.L.,Mountain Diabetes and Endocrine Center | Rappaport J.M.,Mountain Diabetes and Endocrine Center | Hale C.B.,Mountain Diabetes and Endocrine Center | And 2 more authors.
Endocrine Practice | Year: 2013

Objective: To evaluate the long-term efficacy and safety of U-500 insulin administered via continuous subcutaneous insulin infusion (CSII) in patients with insulin-resistant type 2 diabetes and high insulin requirements.Methods: We retrospectively reviewed the effects of U-500 insulin administered via CSII on durability of glycemic control (HbA1c), body weight, total daily insulin dose, and incidence of hypoglycemia in 59 patients with insulin-resistant type 2 diabetes (duration of treatment 1 to 9.5 years; mean treatment duration 49 months). All variables were analyzed by 1-way analysis of variance (ANOVA) from pre-U-500 baseline to time points from 3 to 114 months.Results: After 3 months of U-500 insulin use, hemoglobin A1c dropped significantly from a mean baseline of 8.3% to a mean value of 7.3% (P = .003), and this improvement was sustained for over 66 months of use. There was no significant overall change in body weight or total daily insulin dose over time with the use of U-500 insulin. For those subjects who did gain weight, there was a parallel increase in insulin dose that correlated with weight gain. The overall incidence of severe hypoglycemia was low over the study period, with a mean occurrence of 0.1 episodes per patient per year.Conclusions: U-500 insulin is safe and effective for extended use (up to 9.5 years) in patients with insulin-resistant type 2 diabetes who require high insulin doses, and provides sustained glycemic control without causing excessive weight gain. © 2013 AACE.


Rodbard H.W.,Endocrine and Metabolic Consultants | Gough S.,University of Oxford | Lane W.,Mountain Diabetes and Endocrine Center | Korsholm L.,Novo Nordisk AS | And 2 more authors.
Endocrine Practice | Year: 2014

Objective: This meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials.Methods: This meta-analysis compared glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using >60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26- or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose >56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00:01 and 05:59 AM.Results: More than one-third of IDeg- (35%) and IGlar- (34%) treated T2D subjects required >60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA1c values (estimated treatment difference [ETD] IDeg - IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: -5.9 mg/dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P<.01).Conclusion: In this post hoc meta-analysis, more than 30% of subjects with T2D required >60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar. Copyright © 2014 AACE.


Lane W.,Mountain Diabetes and Endocrine Center | Weinrib S.,Mountain Diabetes and Endocrine Center | Rappaport J.,Mountain Diabetes and Endocrine Center | Hale C.,Mountain Diabetes and Endocrine Center
Diabetes, Obesity and Metabolism | Year: 2014

Patients with type 2 diabetes and insulin resistance may require high insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce insulin requirement while reducing insulin-associated weight gain [1,2]. The effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has not been studied in a prospective trial. This trial evaluated the effect of the addition of liraglutide to high-dose intensive insulin therapy compared with standard insulin up-titration in obese insulin-resistant patients with type 2 diabetes requiring high-dose insulin therapy. Methods: Thirty-seven subjects with type 2 diabetes requiring >100 units of insulin daily administered either by continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDIs) with or without metformin were randomized to receive either liraglutide plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was initiated at 0.6mg subcutaneously (sq) per day and increased to either 1.2 or 1.8mg daily in combination with intensive insulin therapy. Controls received intensive insulin up-titration only. Results: At 6months, subjects receiving liraglutide plus insulin experienced statistically significant reductions in HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose monitor (CGM) compared with the control group receiving insulin only. Conclusions: Adding liraglutide to intensive high-dose (basal/bolus) insulin therapy results in greater improvement in glycaemic control than insulin therapy alone, with additional benefits of weight loss and reduced GV. © 2014 John Wiley and Sons Ltd.


Weinrib S.L.,Mountain Diabetes and Endocrine Center | Lane W.S.,Mountain Diabetes and Endocrine Center | Rappaport J.M.,Mountain Diabetes and Endocrine Center
Endocrine Practice | Year: 2012

Objective: To describe the range of differentiated thyroid cancer (DTC) cases, disease complexity, and treatment outcomes seen in our 3-physician community-based general endocrine practice during an 8-year period in order to make comparisons with published cohorts from university settings.Methods: Medical records of patients with DTC treated between 2002 and 2009 at Mountain Diabetes and Endocrine Center (Asheville, North Carolina) were reviewed. Pathologic features, staging, and disease status at last contact were determined. Multivariate analyses of adverse prognostic risk factors at diagnosis, recombinant human thyroid-stimulating hormone use, and radioiodine use were compared with the ultimate outcome of patients.Results: We treated a total of 167 patients with DTC during the study period (mean age at diagnosis, 44.4 years; mean duration of follow-up, 6.2 years). In our study cohort, 88.6% had papillary thyroid cancer, 74% had stage I disease, and 32.4% of those with papillary thyroid cancer had microscopic tumors (≤1 cm). Remission occurred in 67.1%, 17.1% had persistent disease, and 11.8% were indeterminate for remission; non-thyroid cancer death occurred in 2.6% and disease-specific death in 1.3%. The mean number of adverse prognostic risk factors per patient was 2.0 in those with remission and 4.7 in those with persistent disease.Conclusion: Community-based endocrinologists evaluate the full spectrum of thyroid cancer disease complexity and can achieve excellent outcomes. In our current study group, disease persistence and disease-specific death occurred in 17.1% and 1.3%, respectively. Individualization of care based on prognostic variables guided our diagnostic and therapeutic decisions. Copyright © 2012 AACE.


Lane W.,Mountain Diabetes and Endocrine Center | Weinrib S.,Mountain Diabetes and Endocrine Center | Rappaport J.,Mountain Diabetes and Endocrine Center
Diabetes Technology and Therapeutics | Year: 2011

Background: Patients with insulin-treated type 2 diabetes and high insulin requirements are subject to undesirable treatment-related weight gain. These patients would potentially benefit from the insulin-sparing and weight loss benefits of glucagon-like peptide 1 (GLP-1) receptor agonist therapy; however, GLP-1 receptor agonists currently are not approved for use in combination with insulin. We examined the effects of adding liraglutide at a daily dose of 1.2 or 1.8mg to an intensive regimen (either multiple daily injections or continuous subcutaneous insulin infusion) of U-500 insulin on hemoglobin A1c (HbA1c), total daily insulin dose, and weight in 15 patients with type 2 diabetes and high insulin requirements (initial mean daily insulin dose of 192±77 units per day; initial mean weight, 300.9±55.7lbs) in a clinical practice setting. Methods: In this observational case series, we identified 15 patients treated with a combination of U-500 insulin and liraglutide for at least 12 weeks at routine follow-up office visits. The U-500 insulin dose was reduced by 0-30% upon initiation of liraglutide. Insulin doses were subsequently adjusted to optimize glycemic control. Endpoints included change in HbA1c, change in total daily insulin dose, change in weight, and incidence of hypoglycemia. Comparisons of 12-week and baseline values were evaluated by paired two-tailed t tests. Results: At 12 weeks, the reduction in HbA1c from baseline (8.48%) was 1.4% (P=0.0001). Weight fell by an average of 11.2lb (5.1kg) (P=0.0001). Total daily insulin dose was reduced by 28% (P=0.0001). No severe episodes of hypoglycemia occurred. Conclusions: Adding liraglutide to U-500 insulin resulted in significant improvements in glycemic control, weight loss, and reduced insulin requirements in patients with type 2 diabetes and high insulin requirements. © Copyright 2011, Mary Ann Liebert, Inc.


PubMed | Mountain Diabetes and Endocrine Center
Type: Comparative Study | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2012

To describe the range of differentiated thyroid cancer (DTC) cases, disease complexity, and treatment outcomes seen in our 3-physician community-based general endocrine practice during an 8-year period in order to make comparisons with published cohorts from university settings.Medical records of patients with DTC treated between 2002 and 2009 at Mountain Diabetes and Endocrine Center (Asheville, North Carolina) were reviewed. Pathologic features, staging, and disease status at last contact were determined. Multivariate analyses of adverse prognostic risk factors at diagnosis, recombinant human thyroid-stimulating hormone use, and radioiodine use were compared with the ultimate outcome of patients.We treated a total of 167 patients with DTC during the study period (mean age at diagnosis, 44.4 years; mean duration of follow-up, 6.2 years). In our study cohort, 88.6% had papillary thyroid cancer, 74% had stage I disease, and 32.4% of those with papillary thyroid cancer had microscopic tumors (1 cm). Remission occurred in 67.1%, 17.1% had persistent disease, and 11.8% were indeterminate for remission; non-thyroid cancer death occurred in 2.6% and disease-specific death in 1.3%. The mean number of adverse prognostic risk factors per patient was 2.0 in those with remission and 4.7 in those with persistent disease.Community-based endocrinologists evaluate the full spectrum of thyroid cancer disease complexity and can achieve excellent outcomes. In our current study group, disease persistence and disease-specific death occurred in 17.1% and 1.3%, respectively. Individualization of care based on prognostic variables guided our diagnostic and therapeutic decisions.


PubMed | Mountain Diabetes and Endocrine Center
Type: Journal Article | Journal: Diabetes technology & therapeutics | Year: 2011

Patients with insulin-treated type 2 diabetes and high insulin requirements are subject to undesirable treatment-related weight gain. These patients would potentially benefit from the insulin-sparing and weight loss benefits of glucagon-like peptide 1 (GLP-1) receptor agonist therapy; however, GLP-1 receptor agonists currently are not approved for use in combination with insulin. We examined the effects of adding liraglutide at a daily dose of 1.2 or 1.8 mg to an intensive regimen (either multiple daily injections or continuous subcutaneous insulin infusion) of U-500 insulin on hemoglobin A1c (HbA1c), total daily insulin dose, and weight in 15 patients with type 2 diabetes and high insulin requirements (initial mean daily insulin dose of 192 77 units per day; initial mean weight, 300.9 55.7 lbs) in a clinical practice setting.In this observational case series, we identified 15 patients treated with a combination of U-500 insulin and liraglutide for at least 12 weeks at routine follow-up office visits. The U-500 insulin dose was reduced by 0-30% upon initiation of liraglutide. Insulin doses were subsequently adjusted to optimize glycemic control. Endpoints included change in HbA1c, change in total daily insulin dose, change in weight, and incidence of hypoglycemia. Comparisons of 12-week and baseline values were evaluated by paired two-tailed t tests.At 12 weeks, the reduction in HbA1c from baseline (8.48%) was 1.4% (P = 0.0001). Weight fell by an average of 11.2 LB (5.1 KG) (P = 0.0001). Total daily insulin dose was reduced by 28% (P = 0.0001). No severe episodes of hypoglycemia occurred.Adding liraglutide to U-500 insulin resulted in significant improvements in glycemic control, weight loss, and reduced insulin requirements in patients with type 2 diabetes and high insulin requirements.


PubMed | Endocrine and Metabolic Consultants, University of Oxford, Metabolic Institute of America, Novo Nordisk AS and Mountain Diabetes and Endocrine Center
Type: Comparative Study | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2014

This meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials.This meta-analysis compared glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using >60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26- or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose >56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00:01 and 05:59 AM.More than one-third of IDeg- (35%) and IGlar- (34%) treated T2D subjects required >60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA1c values (estimated treatment difference [ETD] IDeg - IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: -5.9 mg/dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P<.01).In this post hoc meta-analysis, more than 30% of subjects with T2D required >60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar.

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