Precision Medicine and Obesity Hurtado A, Maria Daniela; Acosta, Andres
Gastroenterology Clinics of North America,
03/2021, Volume:
50, Issue:
1
Journal Article
Peer reviewed
Open access
The highly variable response to obesity therapies justifies the search for treatment strategies that are best suited to individual patients to enhance their effectiveness and tolerability via ...precision medicine. Precision medicine development in recent years has been driven by the emergence of powerful methods to characterize patients ("omic" assays). Current available information has revealed that there are numerous intermediary processes that contribute to obesity and have provided a framework for partially comprehending the mechanisms behind the heterogeneity of obesity and its clinical consequences. Some of these processes have or are currently being targeted to individualize obesity therapy with some success.
Purpose
The shift towards an obese phenotype in celiac disease (CD) patients increases risk of morbidity and mortality. Bariatric surgery (BS) is the gold standard treatment for obesity. Few studies ...have explored the role of BS in patients with CD. This study aimed to assess the effectiveness and safety of BS in this population.
Material and Methods
This is a retrospective matched case-control (1:5) study of adult patients with confirmed CD who underwent BS at our institution from 1998 to 2018. Demographics, operative data, post-operative outcomes, complications, and nutritional parameters were collected.
Results
Seventy-eight patients (mostly Caucasian females) were included. Thirteen had confirmed CD and were compared with 65 controls. The most common type of BS was the RYGB. The percent of total body weight loss (%TWL) was similar for both groups at 6, 12, 18, 24, and 36 months, with the highest weight loss being at 12 months: %TWL 28.4 (20.2–38.4) for CD,
n
=13; vs. 29.1 (19.6–39.3) for non-CD,
n
=49;
p
=0.8. Obesity-associated co-morbidities greatly and comparably improved in both groups. Patients with CD had no complications after BS. Post-BS malodorous and oily stools were more common among patients with CD (23.1% vs. 4.6%,
p
=0.03). Micronutrient deficiencies were common and comparable among both groups with iron and vitamin D being the most common deficiencies. Gluten-free diet (GFD) non-adherence post-operatively was associated with a higher incidence of post-BS abdominal pain (60.0% vs. 0.0%,
p
=0.012).
Conclusions
BS is safe and effective in patients with CD. Close monitoring is necessary to ensure compliance with GFD and vitamin supplementation.
Key points
• Bariatric surgery leads to significant weight loss in celiac disease (CD) patients.
• Mid- and long-term weight loss does not differ between patients with and without CD.
• Obesity-associated co-morbidities significantly improve after surgery in CD patients.
• The incidence of post-surgical complications is not higher in CD patients.
Summary
Objective
To identify predictors of hypothalamic‐pituitary‐adrenal (HPA) axis recovery interval and severity of glucocorticoid withdrawal symptoms (GWS) in patients undergoing adrenalectomy ...for corticotropin‐independent cortisol excess.
Design
This is a retrospective study of patients with mild autonomous cortisol excess (MACE), moderate and severe Cushing syndrome (CS) who developed adrenal insufficiency after unilateral adrenalectomy between 1998 and 2017.
Results
Adrenalectomy was performed in 81 patients (79% women, median age 52 years IQR 42‐62). HPA axis recovery occurred at a median of 4.3 months (IQR 1.6‐11.4) after adrenalectomy (severe CS vs moderate CS vs MACE: median 11.4 vs 2.8 vs 2.1 months, P < 0.01). Main predictors of HPA axis recovery interval included: preoperative serum cortisol concentration after 1‐mg overnight dexamethasone suppression test >10 μg/dL or >276 nmol/L (9.7 vs 1.3 months if cortisol ≤10 μg/dL or ≤276 nmol/L, P < 0.01); body mass index (for every 3 kg/m2 decrease, glucocorticoid taper increased by 1 month, P < 0.05); age <45 (11.4 vs 2.3 months if ≥45 years, P < 0.05); duration of symptoms prior to diagnosis >1 year (11.4 vs 2.8 months if ≤1 year); moon facies (11.4 vs 2.2 months if no rounding of the face); and myopathy (13.1 vs 2.7 months if no myopathy, P < 0.05). Patients with severe CS had a higher incidence of GWS compared to patients with MACE (66.7% vs 40.0%, P < 0.05) with a median of 1 and 0 events/patient, respectively.
Conclusions
The HPA axis recovery interval was the longest for patients with severe CS. Surprisingly, patients with moderate CS recovered their HPA axis as quickly as those with MACE. Glucocorticoid withdrawal symptoms were observed in all groups, with more events in patients with severe CS. This study emphasizes the need to counsel patients on expectations for HPA axis recovery and address intervention for GWS based on individual preoperative parameters.
Hunger, satiation, postprandial satiety, and hedonic eating constitute key food intake parameters. We aim to study whether these symptoms are associated with gastrointestinal symptoms (GIS) in ...patients with obesity.
This is a cross-sectional study of patients with obesity. Patients completed the following validated biomarkers and questionnaires: hunger was measured via visual analog scale (100 mm) following a standard meal, satiation was measured via ad libitum meal (calories to fullness; kcal), postprandial satiety was measured via gastric emptying scintigraphy (T1/2; mins), and hedonic eating was measured via the Hospital Anxiety and Depression Scale questionnaire. Participants completed the abridged Bowel Disease Questionnaire to evaluate their GIS. We calculated the odds ratios (ORs) adjusted for sex, weight, and age between food intake parameters <25th or >75th percentile observed in a prior cohort of 450 participants with obesity and GIS.
A total of 274 participants (41 ± 10 SD years, 75% females, body mass index 39 ± 8 kg/m2) were included in the analysis. Increased hunger was associated with a lower prevalence of lumpy stools (OR = 0.18, P = .02). Satiation was associated with abdominal pain/discomfort (relieved by defecation OR = 2.4, P = .02 or associated with change in stool consistency OR = 2.92, P < .01), loose/watery stools (OR = 2.09, P = .02), and bloating (OR = 2.49, P < .01). Abnormal postprandial satiety was associated with bloating (OR = 2.26, P < .01) and loose/watery stools (OR = 1.84, P = .04). Hedonic eating was associated with abdominal pain/discomfort with stool frequency change (OR = 2.4, P = .02), >3 bowel movements per day (OR = 1.93, P = .048), bloating (OR = 2.49, P = .01), abdominal pain after meals >1 per month (OR = 4.24, P < .01), and nausea >1 per week (OR = 4.51, P < .01).
Alterations in hunger, satiation, postprandial satiety, and hedonic eating are associated with GIS in patients with obesity.
Precision Medicine and Obesity Sacoto, Daniel; Hurtado, Maria Daniela; Acosta, Andres
Handbook of experimental pharmacology,
2022, Volume:
274
Journal Article
Peer reviewed
Open access
Obesity is a chronic, relapsing, and multifactorial disease, with a rising prevalence and an associated high economic burden. Achieving successful and sustained weight loss outcomes with current ...interventions is challenging. This is due, at least in part, to the disease's heterogenous pathophysiology that is yet to be completely understood. Technological advances and greater capabilities for the extraction and storage of information have facilitated the application of precision medicine. Several precision medicine initiatives have been proposed to improve obesity outcomes. Most of these initiatives are based on -omics technologies. Although the data generated from these technologies have led to developing hypotheses that may explain the underpinnings of obesity, their applicability to the clinical practice is yet to be determined. There are other initiatives that have identified quantitative or qualitative physiologic traits that can be targeted and that could have a more immediate clinical impact. This review aims to provide a perspective of current initiatives for precision medicine for obesity.
Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of ...dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000-2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9-32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL,
< 0.0001) and ACTH (8.3 vs. 16 pg/mL,
< 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.
Chronic non-communicable diseases (CNCD) represent a major cause of morbidity and mortality. Type 2 diabetes mellitus (T2DM) is one of the most prevalent CNCD that is associated with a significant ...medical and economic burden. One of the main modifiable risk factors of T2DM is obesity. Many medications used for T2DM can lead to weight gain, worsening one of the root causes of this disease.
In this clinical review, we study the effect of medications for T2DM on body weight. We used MEDLINE, Google scholar, PubMed, Scopus, and Embase databases to search for relevant studies between 1 January 1950 to 20 September 2022 in English language. Here, we review the most prescribed medications for T2DM and summarize their effect on patients’ body weight. We will also present an expert opinion on a recommended weight-centric approach to treat T2DM.
Multiple T2DM medications have been associated with weight gain. Insulin, sulfonylureas, thiazolidinediones and meglitinides may increase body weight. However, biguanides (e.g., metformin), glucagon-like peptide-1 agonists (e.g., semaglutide, liraglutide, tirzepatide), sodium-glucose cotransporter 2 inhibitors, and amylin analogs (e.g., pramlintide) are associated with significant weight loss. Dipeptidyl peptidase-4 inhibitors are considered weight neutral medications. Experts in the fields of endocrinology and obesity recommend utilizing a weight-centric approach when treating T2DM.
Considering the high prevalence and debilitating complication of T2DM, it is of utmost importance to shift from a weight gain approach (i.e., insulin, sulfonylureas) into a weight loss/neutral one (i.e., GLP-1 agonists, SGLT-2 inhibitors, metformin).
Glucagon-like peptide 1 (GLP-1) receptor agonists have transformed the treatment of type 2 diabetes and obesity. These agents have been associated with varying degrees of delay in gastric emptying, ...and a significant proportion of patients experience digestive side effects.
There have been previous case reports of gastric retention of food and pulmonary aspiration during upper gastrointestinal (GI) endoscopy in the setting of GLP-1 receptor agonist use
; however, the cumulative incidence has not been previously explored.
What is type 2 diabetes? Hurtado, Maria Daniela; Vella, Adrian
Medicine (Abingdon. 1995, UK ed.),
January 2019, 2019-01-00, Volume:
47, Issue:
1
Journal Article
Peer reviewed
Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycaemia. It is associated with reduced life expectancy owing to a greater risk of heart disease, stroke, ...peripheral neuropathy, renal disease, blindness and amputation. The best-known predictors of increased diabetes risk are elevated fasting plasma glucose, elevated 1- and 2-hour plasma glucose after an oral glucose tolerance test, obesity and evidence of impaired insulin action. However, the mechanisms by which people with impaired fasting glucose and/or abnormal glucose tolerance ‘progress’ to overt T2DM are not completely understood. Moreover, T2DM is defined in a ‘negative’ sense (hyperglycaemia not accounted for by autoimmune destruction of islet cells or other known causes). This has two potentially negative consequences: first, T2DM may actually encompass a heterogeneous group of hyperglycaemic disorders with multiple different mechanisms; and second, defining such a complex disease affecting many different metabolic pathways simply in terms of hyperglycaemia may oversimplify the nature of the condition. In this review, we explore some of the mechanisms suggested to underlie T2DM, and attempt to remind readers that hyperglycaemia is only one of its characteristics.
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