Purpose of Review
Weight gain and body fat redistribution are common side effects of many widely used drugs. We summarize recent literature on prevalence data and mechanisms associated with ...drug-induced body fat changes and mechanisms to prevent or treat metabolic side effects.
Recent Findings
The highest prevalence of metabolic complications is seen with antipsychotics and antiretroviral drugs used in the treatment of HIV and may, at least partly, be responsible for the increased risk for co-morbid diseases such as diabetes, steatosis of the liver, and cardiovascular disease. The pathogenetic mechanisms leading to weight gain from antipsychotics are increasingly known and help to unravel the complex interaction that exists between psychopathology and metabolic complications. Although the classic lipodystrophy mainly occurred with older HIV drugs, also with the newer HIV treatment, weight gain seems to be a major side effect.
Summary
Early detection of the metabolic consequences of drugs can lead to an early diagnosis of the complications and their treatment. Different medications, including the newer antidiabetics, are being studied in the therapy of drug-induced obesity. Future research should focus on identifying individuals at risk for metabolic side effects and on early markers to identify individuals with side effects so that timely treatment of metabolic complications can be initiated.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Fear of hypoglycemia and treatment satisfaction both influence therapy adherence. MAGE was a 6-month multicenter, prospective, single-arm, observational study with a 6-month extension conducted in ...Belgium, mainly assessing patient satisfaction with Gla-300 in people ≥18 years, with T2DM for ≥1 year, HbA1c 7.0-10.0%, receiving a basal-bolus insulin regimen for ≥6 months ± oral antidiabetic therapy, and naïve to Gla-300. Primary objective: change of ≥2 points in Diabetes Treatment Satisfaction Questionnaire Status Version (DTSQs) total score (TS) from baseline (BL) to month 6. Secondary objectives included change in: HbA1c, other DTSQs scores, and hypoglycemia fear scale II (HFS-II). The intent-to-treat population comprised 87 patients (Table). Primary endpoint was achieved; DTSQs TS increased by 2.80 (SD: 5.46; p<0.0001; Table). Significant decreases were seen in total HFS-II scores and worry/behavior subscales (all p<0.05). There was no change from BL in HbA1c (p>0.05); however, more patients reached HbA1c <7% at month 12 versus BL (11.5% vs. 0%). Hypoglycemia occurred at a mean (SD) 34.97 (48.28) events per patient-year.
Treatment satisfaction and fear of hypoglycemia significantly improved after switching to Gla-300 in people with T2DM on basal-bolus insulin therapy in a real-life setting.
Disclosure
A.A. Verhaegen: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Sanofi. Speaker's Bureau; Self; Mylan, Novo Nordisk Inc. A. Scheen: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. K.C. Alexandre: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Bruhwyler: Other Relationship; Self; Sanofi. I.M. Colin: None.
Funding
Sanofi
Aims. To evaluate the feasibility and efficacy of a gestational diabetes (GDM) recall register on the long-term screening uptake postpartum and to evaluate the prevalence of prediabetes postpartum. ...Methods. Evaluation of a GDM recall register implemented in 66 obstetrical centers in the northern part of Belgium from 2009 to 2016. Registrants receive yearly reminders to have a fasting plasma glucose test in primary care to timely detect prediabetes. Results. After 6 years, 7269 women were registered. The yearly response rates varied from 74.4% after the first year to 61.8% after the fifth year. The number of women who reported a screening test varied from 67.4% after the first year to 71.9% after the fifth year. Compared to women who responded at least once to a reminder, women who never responded were more often <30 years (41.4% versus 33.9%, p<0.001) and were more often obese (29.3% versus 20.8%, p≤0.001). Over a period of 6 years, 7.3% (CI 6.0%–8.8%) developed diabetes and 27.4% (CI 23.9%–31.0%) developed impaired fasting glycaemia. Conclusion. We show now the long-term feasibility and efficacy of a GDM recall register to stimulate screening postpartum. One-third of women developed prediabetes within 6 years.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
A man in his late 60s with a history of well-controlled type 2 diabetes and hepatic cirrhosis presented to the emergency department due to uncontrollable hyperglycaemia following the initial ...brentuximab vedotin (BV) infusion. BV was initiated as a treatment for mycosis fungoides, a form of cutaneous T-cell lymphoma. The patient was diagnosed with severe hyperglycaemia with ketosis. Empiric treatment with amoxicillin-clavulanic acid, hydration and intravenous insulin infusion was initiated. Hyperglycaemia persisted despite receiving massive amounts of insulin and was corrected only after treatment with high-dose methylprednisolone for suspected type B insulin resistance. Extremely high and difficult-to-treat hyperglycaemia is a rare side effect of BV. Unfortunately, the patient died of upper gastrointestinal bleeding 22 days after discharge. In patients with obesity and/or diabetes mellitus, the blood glucose levels should be carefully monitored when treated with BV.
Purpose of Review
E-cigarette smoking is rapidly increasing, especially in adolescents and adults, although data on their safety or harm is still scarce. There have been few systematic studies of the ...health effects of e-cigarette use and most studies report on the use of e-cigarettes in past or current cigarette smokers. In this paper, we want to summarize cardiovascular effects of e-cigarettes.
Recent Findings
E-cigarettes could cause cardiovascular harm especially by the toxic effects and of the e-liquid and induction of oxidative stress. Nicotine has known effects on cardiovascular function that are not different in e-cigarettes to those in combustible cigarettes. Moreover, vaping nicotine could be the driver for future revival of combustible smoking.
Summary
Although it seems that e-cigarettes are a safer alternative than combustible cigarettes for people that want to stop smoking, toxic effects of the e-liquid can induce an increase in cardiovascular risk. Long-term data of their safety are still scarce or even lacking and most data are generated in studies with active or past regular cigarette smokers. More data on the cardiovascular and metabolic side effects of vaping are warranted in people naïve for smoking combustible cigarettes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
► BoNT-A in the region of the motor end plate zone of the psoas muscle gives muscle atrophy. ► Muscle atrophy after MEP targeted injection is present on MRI after 2 and 6months. ► Injection of the ...psoas muscle in the distal area will not give muscle atrophy.
MEP targeting during BoNT-A injections has been demonstrated to improve outcome. Two injection techniques of the psoas muscle – proximal MEP targeting versus a widely used more distal injection technique – are compared using muscle volume assessment by digital MRI segmentation as outcome measure.
7 spastic diplegic children received injections in both psoas muscles: two different injection techniques randomly in 5 patients, in 2 patients bilateral MEP targeting. MRI images of the psoas were taken before, after 2months and in 3 patients after 6months.
Average post injection volume (in relation to pre-injection volume) for the MEP targeted muscles (9) is 79.5% versus 107.8% in the 5 distal injected psoas muscles (p=0.0033). In all 5 asymmetric injected patients the MEP targeted psoas had a larger volume reduction than the more distal injected psoas muscle. This atrophy remains even 6months after the injection.
This is the first study were a longitudinal follow-up by MRI demonstrates muscle atrophy after BoNT-A in children with CP. Injections in the MEP zone of the muscle, which is the more proximal part of the psoas muscle, cause atrophy in contrary to more distal injections were this atrophy is not observed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Objective: To describe a unique case of a 61-year-old patient presenting with ectopic Cushing syndrome as a paraneoplastic phenomenon due to adrenocorticotropic hormone (ACTH)-secreting bone ...metastasis of an olfactory neuroblastoma (ON).Methods: We report a detailed case, with clinical, biochemical, and imaging findings and compare it with existing literature.Results: A patient with an ON, with subsequent 10-year stable disease after initial craniofacial surgery, presented with paraparesis due to progressively metastasized ON disease located in the thoracic spine. During palliative chemotherapy, severe hypokalemia and muscle weakness developed, being part of paraneoplastic Cushing syndrome. Examination showed that metastatic bone lesions were mostly responsible for the ectopic secretion of ACTH, with just a few ACTH-secreting tumor cells located in the primary tumor. She was treated with a combination of ketoconazole and metyrapone that controlled cortisol levels. However, low potassium levels persisted. Finally, she underwent a bilateral adrenal resection, after which most cushingoid symptoms disappeared. She died 1 month later.Conclusion: Our case shows a growing ON with several bone metastases, which is a rare clinical condition. Moreover, this is the first report that ON is associated with bone metastases that express excessive ACTH secretion (and suggesting dedifferentiation of the primary tumor during chemotherapy treatment). Ectopic Cushing syndrome (with ACTH secreted by ON bone metastasis) can present late in the clinical trajectory. Finally, a bilateral adrenalectomy was needed to correct the life-threatening hypokalemia as part of the ectopic Cushing syndrome.Abbreviations: ACTH adrenocorticotropic hormone; CRH corticotropin-releasing hormone; IPSS inferior petrosal sinus smapling; ON olfactory neuroblastoma
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high‐risk individuals. With ...currently available GLP‐1 RAs, 51%‐79% of subjects achieve an HbA1c target of less than 7.0% and 4%‐27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms ‘glucagon‐like peptide‐1 receptor agonist’, ‘glucagon receptor agonist’, ‘glucose‐dependent insulinotropic peptide’, ‘dual or co‐agonist’, and ‘tirzepatide’. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high‐dose GLP‐1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high‐dose GLP‐1 RAs or tirzepatide, respectively. The glucose‐ and weight‐lowering effects of the GLP‐1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high‐dose GLP‐1 RAs and co‐agonists occurred in 30%‐70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high‐dose GLP‐1 RAs and the dual GLP‐1/glucose‐dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15‐mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Context
Bile acids (BAs) are signaling molecules controlling energy homeostasis that can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin ...resistance (IR), and nonalcoholic steatohepatitis (NASH). However, whether BA alterations contribute to NASH independently of the metabolic status is unclear.
Objective
To assess BA alterations associated with NASH independently of body mass index and IR.
Design and Setting
Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014.
Patients
Obese patients with biopsy-proven NASH (n = 32) and healthy livers (n = 26) were matched on body mass index and homeostasis model assessment of IR.
Main Outcome Measures
Transcriptomic analyses were performed on liver biopsies. Plasma concentrations of 21 BA species and 7α-hydroxy-4-cholesten-3-one, a marker of BA synthesis, were determined by liquid chromatography–tandem mass spectrometry. Plasma fibroblast growth factor 19 was measured by enzyme-linked immunosorbent assay.
Results
Plasma BA concentrations did not correlate with any hepatic lesions, whereas, as previously reported, primary BA strongly correlated with IR. Transcriptomic analyses showed unaltered hepatic BA metabolism in NASH patients. In line, plasma 7α-hydroxy-4-cholesten-3-one was unchanged in NASH. Moreover, no sign of hepatic BA accumulation or activation of BA receptors—farnesoid X, pregnane X, and vitamin D receptors—was found. Finally, plasma fibroblast growth factor 19, secondary-to-primary BA, and free-to-conjugated BA ratios were similar, suggesting unaltered intestinal BA metabolism and signaling.
Conclusions
In obese patients, BA alterations are related to the metabolic phenotype associated with NASH, especially IR, but not liver necroinflammation.
Transcriptomic and metabolomic analyses of bile acid metabolism/signaling reveals no alteration in NASH patients compared with BMI- and insulin resistance–matched controls, unlike in insulin resistance.
Objective: To evaluate real-life lipid and blood pressure (BP) control in a contemporary Belgian population sample treated with at least one lipid-lowering and one antihypertensive drug. Design and ...method: Data was collected through GP questionnaires on 2337 subjects (ATHERO STUDY). Results: A complete set of relevant clinical variables was available for 1706 subjects (61.5% men; mean age 67.9 ± 10.9 years; mean BMI 28.4 ± 4.9 kg/m2), in which CVD, CAD, DM and renal insufficiency were reported respectively in 34.0%; 22.2%, 37.5% and 6.6% of cases. Based on the 2016 EAS/ESC guidelines for the management of dyslipidemias, 68.8% of subjects were classified as very high risk (VHR) and 10.9% as high-risk (HR). Despite the majority (almost 70%) taking > 1 antihypertensive drug, BP was uncontrolled in 44.0% (using the 140/90 mmHg threshold), without clear differences in control across risk strata. Treatment targets from the 2016 LDL-cholesterol guidelines were met in only 24.4% of VHR and 45.7% of HR subjects. For the new LDL-cholesterol targets 2019 ESC/EAS guidelines for the management of dyslipidemias (which came after the data collection) this would be 10.1% and 11.7%% respectively. GP’s estimated adequate BP control in 69.2% and LDL-cholesterol control in 63.4% of cases. Combined BP and LDL-cholesterol control was achieved in 16.1% of VHR and 26.9% of HR subjects. In the VHR group there was a clear gender disparity (11.7% of women compared to 18.6% of men) in achieving adequate combined control. More striking, combined control in those VHR subjects with a clinical condition (1040/1174 subjects) was 17.9% whilst in those with VHR due to risk factor combinations this was only 2.2%. Use of combination lipid-lowering and antihypertensive drug combinations was low (1.8%) whilst 66.5% of subjects were potential candidates. Conclusions: In GP practices, target achievement was very low for BP and even more so for LDL-cholesterol prevention targets amongst VHR patients, especially in those associated to risk factor combinations rather than more easily recognizable clinical conditions. There was a clear disparity between GPs’ estimates of risk factor control/target achievement and real-life figures in GP practices.
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