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PURPOSE OF REVIEW: Malabsorption and malnutrition are common gastrointestinal manifestations clinicians face, requiring diagnostic workup for effective diagnosis and management of the underlying cause. This review discusses recent advances in diagnostic approaches to malabsorption and maldigestion of macronutrients - lipids, proteins, and carbohydrates. We highlight underrecognized causes, available testing modalities, and ongoing diagnostic unmet needs. RECENT FINDINGS: Innovations in the diagnostic landscape are enhancing our understanding of malabsorption syndromes. Stool collection and handling is uncomfortable and commonly avoided. The objective quantification of stool lipids, bile acids, and gut enzymes is therefore underused in the diagnosis and management of common disorders such as exocrine pancreatic insufficiency, bile acid diarrhea, protein-losing enteropathy, and more. We review the recent advancements in spot quantification of stool fat and bile acid content, endoscopic imaging techniques such as endocytoscopy, confocal laser endomicroscopy, and optical coherence tomography and the future place in clinical practice. SUMMARY: Malabsorption and maldigestion represent significant challenges in clinical nutrition and gastroenterology. Through the integration of advanced diagnostic techniques, clinicians will be better equipped to tailor therapy and monitor treatment response, ultimately improving patient health outcomes. This review underscores the critical role of innovative diagnostic tools in accurately detecting and effectively managing gastrointestinal disorders linked to nutritional status.
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Síndromes de Malabsorción , Desnutrición , Estado Nutricional , Humanos , Síndromes de Malabsorción/diagnóstico , Desnutrición/diagnóstico , Heces , Ácidos y Sales Biliares/metabolismo , Tracto GastrointestinalRESUMEN
AIM: To examine the impact of increased hepatic glucose production (HGP) on the decrease in plasma glucose concentration caused by empagliflozin in individuals living with diabetes and in nondiabetic individuals. METHODS: A total of 36 individuals living with diabetes and 34 nondiabetic individuals were randomized to receive, in double-blind fashion, empagliflozin or matching placebo in a 2:1 treatment ratio. Following an overnight fast, HGP was measured with 3-3 H-glucose infusion before, at the start of, and 3 months after therapy with empagliflozin. RESULTS: On Day 1 of empagliflozin administration, the increase in urinary glucose excretion (UGE) in individuals with normal glucose tolerance was smaller than in those with impaired glucose tolerance and those living with diabetes, and was accompanied by an increase in HGP in all three groups. The amount of glucose returned to the systemic circulation as a result of the increase in HGP was smaller than that excreted by the kidney during the first 3 h after empagliflozin administration, resulting in a decrease in fasting plasma glucose (FPG) concentration. After 3 h, the increase in HGP was in excess of UGE, leading to a small increase in plasma glucose concentration, which reached a new steady state. After 12 weeks, the amount of glucose returned to the circulation due to the empagliflozin-induced increase in HGP was comparable with that excreted by the kidney in all three groups. CONCLUSION: The balance between UGE and increase in HGP immediately after sodium-glucose cotransporter-2 (SGLT2) inhibition determined the magnitude of decrease in FPG and the new steady state which was achieved. After 12 weeks, the increase in HGP caused by empagliflozin closely matched the amount of glucose excreted by the kidneys; thus, FPG level remained stable despite the continuous urinary excretion of glucose caused by SGLT2 inhibition.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Compuestos de Bencidrilo/uso terapéutico , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/metabolismo , Glucósidos , Hipoglucemiantes , Transportador 2 de Sodio-Glucosa , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
BACKGROUND: Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. METHODS: ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjects received 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. RESULTS: Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p < 0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p < 0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. CONCLUSIONS: In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.
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Intolerancia a la Glucosa , Hiperinsulinismo , Resistencia a la Insulina , Hormonas Peptídicas , Estado Prediabético , Humanos , Glucemia/metabolismo , Intolerancia a la Glucosa/metabolismo , Proteína 8 Similar a la Angiopoyetina , Insulina/metabolismo , Glucosa/metabolismo , Ayuno , Ingestión de Alimentos , Insulina Regular Humana , Nutrientes , Resistencia a la Insulina/fisiologíaRESUMEN
AIM: To examine the efficacy of glucose-lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years. RESULTS: Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance. CONCLUSION: Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Qatar/epidemiologíaRESUMEN
AIM: To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin â glipizide â glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. METHODS: Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat. RESULTS: At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (P = .0006). Twenty-seven of 39 subjects (69%) receiving conventional therapy had grade 2/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (P = .0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (P = .04). Conventional therapy subjects had more liver fat (MRI-PDFF) than triple therapy (12.9% vs. 8.8%, P = .03). The severity of steatosis (CAP) (r = 0.42, P < .001) and fibrosis (LSM) (r = -0.48, P < .001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS. CONCLUSIONS: At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis-4, and AST/ALT ratio) have limited value in predicting response to therapy.
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Diabetes Mellitus Tipo 2 , Metformina , Enfermedad del Hígado Graso no Alcohólico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Exenatida , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Metformina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Pioglitazona/uso terapéutico , PrevalenciaRESUMEN
Intra-abdominal pressure (IAP) affects cardio-respiratory and hemodynamic parameters and can be measured directly or indirectly by measuring gastric or urinary bladder pressure. The aim of this study was to investigate the correlation between IAP, gastric pressure and urinary bladder pressure in patients with morbid obesity, at normal and elevated levels of IAP in two positions. As well, to examine the effects of increasing IAP and patient's position on hemodynamic and respiratory parameters. Twelve patients undergoing laparoscopic bariatric surgery were included. IAP, gastric pressure, and urinary bladder pressure were measured while patients were in the supine position and after 45° anti-Trendelenburg tilt. Mean inspiratory pressure, peak inspiratory pressure, and tidal volume were recorded and assessed. In supine position; directly measured IAP was 9.1 ± 1.8 mmHg, compared to 10 ± 3.6 and 8.9 ± 2.9 mmHg in the stomach and bladder, respectively. Increasing IAP to 15 mmHg resulted in an increased gastric pressure of 17 ± 3.8 mmHg, and urinary bladder pressure of 14.8 ± 3.9 mmHg. Gastric and urinary bladder pressures strongly correlated with IAP (R = 0.875 and 0.847, respectively). With 45° anti-Trendelenburg tilt; directly measured IAP was 9.4 ± 2.2 mmHg, and pressures of 10.8 ± 3.8 mmHg and 9.2 ± 3.8 mmHg were measured in the stomach and the bladder, respectively. Increasing IAP to 15 mmHg resulted in elevating gastric and bladder pressures to 16.6 ± 5.3 and 13.3 ± 4 mmHg, respectively. Gastric and urinary bladder pressures had good correlation with IAP (R = 0.843 and 0.819, respectively). Changing patient position from supine to 45° anti-Trendelenburg position resulted in decreased mean and peak inspiratory pressures, and increased tidal volume. Basal IAP is high in patients with morbid obesity. IAP shows positive correlation to gastric and urinary bladder pressures at both normal and elevated levels of IAP. Anti-Trendelenburg tilt of mechanically ventilated morbidly obese patients resulted in favorable effects on respiratory parameters.Trial Registration: The study was retrospectively registered in the NIH registry. Registration number is pending.
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Abdomen , Obesidad Mórbida , Presión , Estómago , Vejiga Urinaria , Humanos , Obesidad Mórbida/cirugíaRESUMEN
AIM: To identify predictors of response to glucose-lowering therapy in patients with new-onset diabetes and very high HbA1c (>10%). METHODS: The study included EDICT participants with an initial HbA1c of more than 10% (N = 104). All subjects received a 75-g oral glucose tolerance test (OGTT) before initiation of therapy, and then were randomized to receive: (a) initial triple therapy with metformin, pioglitazone and exenatide versus (b) stepwise conventional therapy with metformin followed by glipizide and then glargine insulin to reduce HbA1c to less than 6.5%. Insulin secretion and insulin resistance were calculated with OGTT-derived indices. RESULTS: Sixty-one per cent of participants in the conventional therapy group achieved HbA1c of less than 6.5% at 6 months without need of insulin therapy compared with 78% in the triple therapy group (P = NS). Insulin secretion at baseline was the strongest predictor of subjects who did not require insulin therapy; a cut point of CPEP120 /CPEP0 -the ratio between plasma C-peptide concentration at 120 minutes during the OGTT and fasting plasma C-peptide concentration-of more than 1.7 predicted subjects who achieved the treatment target without insulin, irrespective of the fasting plasma glucose (FPG) concentration and whether or not they were started on conventional or triple therapy. Subjects with a CPEP120 /CPEP0 of less than 1.7 plus FPG of 269 mg/dL or less (≤14.9 mmoL/L) also achieved the treatment goal with triple therapy. CONCLUSION: Insulin secretion in response to a 75-g OGTT predicts the need for insulin therapy at the time of type 2 diabetes (T2D) diagnosis. A cut point of 1.7 of CPEP120 /CPEP0 provides a useful clinical tool to individualize glucose-lowering therapy in patients with new-onset T2D and HbA1c of more than 10%.
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Diabetes Mellitus Tipo 2 , Insulina , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Secreción de InsulinaRESUMEN
OBJECTIVE: To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin. RESEARCH DESIGN AND METHODS: Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end. Hepatic glucose production before the start of therapy was measured with 3-3H-glucose. RESULTS: Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants receiving placebo (P < 0.007 with ANOVA). The decrease in liver fat was comparable in both individuals with diabetes and those without (2.75% ± 0.81% and 1.93% ± 0.78%, respectively; P = NS). The decrease in hepatic fat content caused by empagliflozin was strongly correlated with baseline liver fat content (r = -0.62; P < 0.001), decrease in body weight (r = 0.53; P < 0.001), and improvement in insulin sensitivity (r = -0.51; P < 0.001) but was not related to the decrease in fasting plasma glucose or HbA1c or the increase in hepatic glucose production. CONCLUSIONS: Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease in plasma glucose concentration and is strongly related to the decrease in body weight and improvement in insulin sensitivity.
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Diabetes Mellitus Tipo 2 , Glucósidos , Resistencia a la Insulina , Humanos , Hipoglucemiantes/uso terapéutico , Glucemia/metabolismo , Hígado/metabolismo , Compuestos de Bencidrilo , Peso Corporal , Método Doble CiegoRESUMEN
OBJECTIVE: To examine the mechanisms responsible for the increase in glucose and ketone production caused by empagliflozin in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Twelve subjects with T2DM participated in two studies performed in random order. In study 1, endogenous glucose production (EGP) was measured with 8-h infusion of 6,6,D2-glucose. Three hours after the start of 6,6,D2-glucose infusion, subjects ingested 25 mg empagliflozin (n = 8) or placebo (n = 4), and norepinephrine (NE) turnover was measured before and after empagliflozin ingestion with 3H-NE infusion. Study 2 was similar to study 1 but performed under pancreatic clamp conditions. RESULTS: When empagliflozin was ingested under fasting conditions, EGP increased by 31% in association with a decrease in plasma glucose (-34 mg/dL) and insulin (-52%) concentrations and increases in plasma glucagon (+19%), free fatty acid (FFA) (+29%), and ß-hydroxybutyrate (+48%) concentrations. When empagliflozin was ingested under pancreatic clamp conditions, plasma insulin and glucagon concentrations remained unchanged, and the increase in plasma FFA and ketone concentrations was completely blocked, while the increase in EGP persisted. Total-body NE turnover rate was greater in subjects receiving empagliflozin (+67%) compared with placebo under both fasting and pancreatic clamp conditions. No difference in plasma NE concentration was observed in either study. CONCLUSIONS: The decrease in plasma insulin and increase in plasma glucagon concentration caused by empagliflozin is responsible for the increase in plasma FFA concentration and ketone production. The increase in EGP caused by empagliflozin is independent of the change in plasma insulin or glucagon concentrations and is likely explained by the increase in NE turnover.
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Diabetes Mellitus Tipo 2 , Glucosa , Humanos , Glucosa/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucagón , Insulina/uso terapéutico , Cetonas/uso terapéutico , Norepinefrina/uso terapéutico , Glucemia , Ácidos Grasos no EsterificadosRESUMEN
OBJECTIVES: This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections. METHODS: This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement. RESULTS: Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching. CONCLUSIONS: TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary.