Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant

Abstract Introduction Disorders of glucose metabolism are a serious acromegaly comorbidity and may be differently impacted by medical treatments of acromegaly. In this retrospective longitudinal multicenter study, we investigated the outcome of glucose metabolism and its predictors in patients treated with Pasireotide LAR (PAS-LAR) alone or in combination with Pegvisomant (PAS-LAR + Peg-V). Subjects and methods Acromegaly patients treated continously with PAS-LAR or PAS-LAR + Peg-V for at least 6 months. Results Forty patients (25 females, 15 males) were enrolled. At last visit, 27/40 patients (67.5%) reached biochemical control of acromegaly. Overall, glucose metabolism improved in 3 (all in PAS-LAR + Peg-V; 7.5%), worsened in 26 (65%) and remained unchanged in 11 patients (27.5%). Glucose metabolism worsened in 25 patients (73.5%) treated with PAS-LAR and in a single patient (16.7%) treated with PAS-LAR + Peg-V (p < 0.001). Among patients treated with Pas-LAR alone, GH at baseline was higher in those with worsening of glucose metabolism (p = 0.04) as compared to those with stable glucose status. A significantly higher reduction of HbA1c was observed in patients treated with PAS-LAR + Peg-V, as compared with those treated with PAS-LAR alone (p = 0.005). Conclusions Our data confirmed that glucose metabolism in patients treated with PAS-LAR is often worsened, and may be predicted by entity of baseline GH hypersecretion and by the dose of PAS-LAR. Moreover, our data, although limited by small numbers, may suggest that the combination treatment PAS-LAR + Peg-V can improve glucose homeostasis in selected patients.

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Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

Journal of Endocrinology ◽

10.1530/joe-18-0279 ◽

2018 ◽

Vol 239 (3) ◽

pp. 313-324 ◽

Cited By ~ 9

Author(s):

Lewin Small ◽

Henry Gong ◽

Christian Yassmin ◽

Gregory J Cooney ◽

Amanda E Brandon

Keyword(s):

Glucose Metabolism ◽

Ambient Temperature ◽

Fat Mass ◽

Glucose Homeostasis ◽

Dietary Intervention ◽

Whole Body ◽

Housing Temperature ◽

Brown Adipose ◽

Normal Chow ◽

Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

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Faculty Opinions recommendation of Rituximab and subcutaneous 2-chloro-2'-deoxyadenosine combination treatment for patients with Waldenstrom macroglobulinemia: clinical and biologic results of a phase II multicenter study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.4957957.4890058 ◽

2010 ◽

Author(s):

Xavier Leleu

Keyword(s):

Phase Ii ◽

Multicenter Study ◽

Combination Treatment ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia

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Study Designs for Evaluation of Combination Treatment: Focus On Individual Patient Benefit

10.20944/preprints202201.0064.v1 ◽

2022 ◽

Author(s):

Martin C. Michel ◽

David Staskin

Keyword(s):

Combination Treatment ◽

Therapeutic Response ◽

Single Patient ◽

Patient Benefit ◽

Reasonable Expectation ◽

Treatment Focus ◽

Urinary Tract Symptoms ◽

Functional Urology ◽

Study Designs ◽

Lower Urinary

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

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Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

Cardiovascular Diabetology ◽

10.1186/1475-2840-9-83 ◽

2010 ◽

Vol 9 (1) ◽

pp. 83 ◽

Cited By ~ 25

Author(s):

Maria Pallayova ◽

Kimberley E. Steele ◽

Thomas H. Magnuson ◽

Michael A. Schweitzer ◽

Nathan R. Hill ◽

...

Keyword(s):

Sleep Apnea ◽

Glucose Metabolism ◽

Glucose Homeostasis ◽

Impaired Glucose Metabolism ◽

Obese Adults

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Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice

AJP Renal Physiology ◽

10.1152/ajprenal.00111.2021 ◽

2021 ◽

Author(s):

Yuika Osada ◽

Shunsaku Nakagawa ◽

Kanako Ishibe ◽

Shota Takao ◽

Aimi Shimazaki ◽

...

Keyword(s):

Glucose Metabolism ◽

Glucose Homeostasis ◽

Phosphoenolpyruvate Carboxykinase ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Kidney Injury ◽

Short Chain Fatty Acids ◽

Glucose Levels ◽

The Impact

Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that the bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. The mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, the renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion (IR). Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to IR injury.

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Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00356.2020 ◽

2021 ◽

Author(s):

Camille Marciniak ◽

Oscar Chávez-Talavera ◽

Robert Caiazzo ◽

Thomas Hubert ◽

Lorea Zubiaga ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Body Weight ◽

Glucose Metabolism ◽

Glucose Homeostasis ◽

Body Weight Loss ◽

Metabolic Effects ◽

One Anastomosis Gastric Bypass ◽

Alimentary Limb ◽

The Common

Background/Objectives: The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the One Anastomosis Gastric Bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces stronger beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the biliary and common limbs in the weight-loss and metabolic effects that occur upon OAGB. Subjects/Methods: OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen-like minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. Results: OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Conclusions: Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss.

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Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP)

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000942 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000942

Author(s):

Mouna El-Mehdi ◽

Saloua Takhlidjt ◽

Fayrouz Khiar ◽

Gaëtan Prévost ◽

Jean-Luc do Rego ◽

...

Keyword(s):

Glucose Metabolism ◽

Pancreatic Islets ◽

Glucose Homeostasis ◽

Gene Knockout ◽

Hepatic Glucose Production ◽

Biologically Active ◽

Mutant Mice ◽

Insulin Production ◽

Coding Region ◽

The Impact

Introduction26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.Research design and methods26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated.ResultsOur data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibited an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. Two-dimensional and three-dimensional immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa−/− mice as compared with the wild-type littermates.ConclusionDisruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis, with in particular a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.

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