Clinical Overview > Topic
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Search for other papers by Ana Munhoz in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Search for other papers by Cláudia Paiva in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Obesity Treatment Center - Unidade de Tratamento Cirúrgico de Obesidade (UTCO), Porto, Portugal
CAC ICBAS-CHP, Porto, Portugal
I3S, Glycobiology and Cancer Research, Porto, Portugal
Search for other papers by Isabel Mesquita in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Obesity Treatment Center - Unidade de Tratamento Cirúrgico de Obesidade (UTCO), Porto, Portugal
Search for other papers by Teresa Correia in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Obesity Treatment Center - Unidade de Tratamento Cirúrgico de Obesidade (UTCO), Porto, Portugal
Search for other papers by Mário Marcos in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Obesity Treatment Center - Unidade de Tratamento Cirúrgico de Obesidade (UTCO), Porto, Portugal
Search for other papers by Jorge Santos in
Google Scholar
PubMed
Department of Digestive and Extra-Digestive Surgery, Porto, Portugal
Obesity Treatment Center - Unidade de Tratamento Cirúrgico de Obesidade (UTCO), Porto, Portugal
CAC ICBAS-CHP, Porto, Portugal
Search for other papers by Paulo Soares in
Google Scholar
PubMed
Summary
Bariatric surgery is increasingly being accepted as a viable treatment for managing the growing obesity epidemic. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures. Perforated duodenal ulcer following RYGB is a rare condition with a low incidence. We report a case of a patient with a perforated duodenal ulcer post RYGB, and the surgical approach. A 66-year-old man with hypertension and a history of laparoscopic RYGB for class III obesity was admitted to the emergency department with severe epigastric pain radiating to the right side of his abdomen and right shoulder, associated with nausea and vomiting. Computed tomography (CT) showed intraperitoneal free fluid, a thickened wall of the duodenum and free air, duodenal perforation was suspected. The patient underwent exploratory laparoscopy that revealed a perforated duodenal ulcer that was closed with an absorbable barbed suture and omental patch. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis, and clinicians should be aware of and have a low threshold for diagnostic laparoscopy.
Learning points
-
Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in bariatric surgery.
-
Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis.
-
The pathophysiology of this perforation is not clear, but several mechanisms have been proposed. Helicobacter pylori has been implicated.
-
Clinicians should be aware and have a low threshold for diagnostic laparoscopy for a patient who has acute abdominal pain after RYGB, despite negative diagnostic measures.
Search for other papers by Kiveum Kim in
Google Scholar
PubMed
Search for other papers by Jacob Lim Greenspan in
Google Scholar
PubMed
Search for other papers by Shaheen Mehrara in
Google Scholar
PubMed
Search for other papers by David Wynne in
Google Scholar
PubMed
Search for other papers by Elizabeth Ennis in
Google Scholar
PubMed
Summary
Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication.
Learning points
-
Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially.
-
The incidence is 0.1–0.3% of all post Roux-en-Y gastric bypass patients.
-
The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases.
-
Pathological specimen of pancreas will show diffuse hypertrophy of beta cells.
-
Management includes acarbose and total or subtotal pancreatectomy, which can be curative.
-
With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.
Search for other papers by Maha Khalil Abass in
Google Scholar
PubMed
Search for other papers by Aisha Al Shamsi in
Google Scholar
PubMed
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
Search for other papers by Iftikhar Jan in
Google Scholar
PubMed
Search for other papers by Mohammed Suhail Yasin Masalawala in
Google Scholar
PubMed
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
Search for other papers by Asma Deeb in
Google Scholar
PubMed
Summary
The most frequent causes of pancreatitis classically have been known to be gallstones or alcohol. However, genetics can also play a key role in predisposing patients to both chronic and acute pancreatitis. The serine protease inhibitor Kazal type 1 (SPINK 1) gene is known to be strongly associated with pancreatitis. Patients with these underlying genetic mutations can have severe diseases with a high morbidity rate and frequent hospitalization. We report an Arab girl who presented with acute pancreatitis at the age of 7 years progressing to recurrent chronic pancreatitis over a few years. She had severe obesity from the age of 4 years and developed type 2 diabetes at the age of 12. She had a normal biliary system anatomy. Genetic analysis showed that she had combined heterozygous mutations in the SPINK1 gene (SPINK1, c.101A>G p.(Asn34Ser) and SPINK1, c.56-37T>C). Her parents were first-degree cousins, but neither had obesity. Mother was detected to have the same mutations. She had type 2 diabetes but never presented with pancreatitis. This case is the first to be reported from the Arab region with these combined mutations leading to recurrent chronic pancreatitis. It illustrates the importance of diagnosing the underlying genetic mutation in the absence of other known causes of pancreatitis. Considering the absence of pancreatitis history in the mother who did not have obesity but harboured the same mutations, we point out that severe obesity might be a triggering factor of pancreatitis in the presence of the mutations in SPINK1 gene in this child. While this is not an assumption from a single patient, we show that not all carriers of this mutation develop the disease even within the same family. Triggering factors like severe obesity might have a role in developing the disease.
Learning points
-
Acute recurrent pancreatitis and chronic pancreatitis are uncommon in children but might be underdiagnosed.
-
Biliary tract anomalies and dyslipidaemias are known causative factors for pancreatitis, but pancreatitis can be seen in children with intact biliary system.
-
Genetic diagnosis should be sought in children with pancreatitis in the absence of known underlying predisposing factors.
-
SPINK1 mutations can predispose to an early-onset severe recurrent pancreatitis and acute pancreatitis.
Search for other papers by Livia Lugarinho Correa in
Google Scholar
PubMed
Search for other papers by Priscila Alves Medeiros de Sousa in
Google Scholar
PubMed
Search for other papers by Leticia Dinis in
Google Scholar
PubMed
Search for other papers by Luana Barboza Carloto in
Google Scholar
PubMed
Search for other papers by Maitane Nuñez-Garcia in
Google Scholar
PubMed
Search for other papers by Ignacio Sajoux in
Google Scholar
PubMed
Search for other papers by Sidney Senhorini in
Google Scholar
PubMed
Summary
There is a close association between obesity and type 2 diabetes (T2D). The value of weight loss in the management of patients with T2D has long been known. Loss of 15% or more of body weight can have a disease-modifying effect in people with diabetes inducing remission in a large proportion of patients. Very low-carbohydrate ketogenic diets (VLCKDs) have been proposed as an appealing nutritional strategy for obesity management. The diet was shown to result in significant weight loss in the short, intermediate, and long terms and improvement in body composition parameters as well as glycemic and lipid profiles. The reported case is a 35-year-old man with obesity, dyslipidemia, and T2D for 5 years. Despite the use of five antidiabetic medications, including insulin, HbA1c was 10.1%. A VLCKD through a commercial multidisciplinary weight loss program (PnK method) was prescribed and all medications were discontinued. The method is based on high-biological-value protein preparations and has 5 steps, the first 3 steps (active stage) consist of a VLCKD (600–800 kcal/d) that is low in carbohydrates (<50 g daily from vegetables) and lipids. The amount of proteins ranged between 0.8 and 1.2 g/kg of ideal body weight. After only 3 months, the patient lost 20 kg with weight normalization and diabetes remission, and after 2 years of follow-up, the patient remained without the pathologies. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.
Learning points
-
Obesity and type 2 diabetes (T2D) are conditions that share key pathophysiological mechanisms.
-
Loss of 15% or more of body weight can have a disease-modifying effect in people with T2D inducing remission in a large proportion of patients.
-
Diabetes remission should be defined as a return of HbA1c to <6.5% and which persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy.
-
The very low-carbohydrate ketogenic diet (VLCKD) is a nutritional approach that has significant beneficial effects on anthropometric and metabolic parameters.
-
Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.
Search for other papers by Carolina Chaves in
Google Scholar
PubMed
Search for other papers by Teresa Kay in
Google Scholar
PubMed
Search for other papers by João Anselmo in
Google Scholar
PubMed
Summary
Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.
Learning points
-
The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.
-
Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.
-
Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.
Search for other papers by Alejandra Perez-Montes de Oca in
Google Scholar
PubMed
Search for other papers by Silvia Pellitero in
Google Scholar
PubMed
Search for other papers by Manel Puig-Domingo in
Google Scholar
PubMed
Summary
Hypoglycemia is an uncommon clinical problem in non-diabetic patients or patients not being treated for diabetes mellitus. It is a rare, but well-established complication of bariatric surgery and, in some cases, it can be the only symptom of another medical problem. A 50-year-old woman with a history of partially recovered hypopituitarism after transsphenoidal surgery for a non-functioning pituitary macroadenoma complained about symptomatic hypoglycemia after sleeve gastrectomy surgery. Our initial studies failed to determine the cause for these episodes and treatment with acarbose (suspecting a dumping syndrome) was not helpful. Finally, laboratory findings revealed growth hormone (GH) deficiency. The patient received treatment with GH, with the resolution of symptoms after 3 months of treatment. Our case suggests that all causes of hypoglycemia should be considered and studied after bariatric surgery. An improvement in insulin-resistance following bariatric surgery can trigger clinical manifestations of GH deficiency.
Learning points:
-
Postprandial hypoglycemia after bariatric surgery is usually due to dumping syndrome.
-
Even after bariatric surgery, all causes of hypoglycemia should be considered and studied.
-
After significant weight loss, insulin sensitivity is usually restored and can trigger clinical manifestations of GH deficiency.
-
Hypoglycemia is a rare symptom of GH deficiency.
Division of Endocrinology and Metabolism, Dokuz Eylul University, Izmir, Turkey
Search for other papers by Baris Akinci in
Google Scholar
PubMed
Search for other papers by Rasimcan Meral in
Google Scholar
PubMed
Search for other papers by Diana Rus in
Google Scholar
PubMed
Search for other papers by Rita Hench in
Google Scholar
PubMed
Search for other papers by Adam H Neidert in
Google Scholar
PubMed
Search for other papers by Frank DiPaola in
Google Scholar
PubMed
Search for other papers by Maria Westerhoff in
Google Scholar
PubMed
Search for other papers by Simeon I Taylor in
Google Scholar
PubMed
Search for other papers by Elif A Oral in
Google Scholar
PubMed
Summary
A patient with atypical partial lipodystrophy who had a transient initial response to metreleptin experienced acute worsening of her metabolic state when neutralizing antibodies against metreleptin appeared. Because her metabolic status continued to deteriorate, a therapeutic trial with melanocortin-4 receptor agonist setmelanotide, that is believed to function downstream from leptin receptor in the leptin signaling system, was undertaken in an effort to improve her metabolic status for the first time in a patient with lipodystrophy. To achieve this, a compassionate use (investigational new drug application; IND) was initiated (NCT03262610). Glucose control, body fat by dual-energy X-ray absorptiometry and MRI, and liver fat by proton density fat fraction were monitored. Daily hunger scores were assessed by patient filled questionnaires. Although there was a slight decrease in hunger scales and visceral fat, stimulating melanocortin-4 receptor by setmelanotide did not result in any other metabolic benefit such as improvement of hypertriglyceridemia or diabetes control as desired. Targeting melanocortin-4 receptor to regulate energy metabolism in this setting was not sufficient to obtain a significant metabolic benefit. However, complex features of our case make it difficult to generalize these observations to all cases of lipodystrophy. It is still possible that melanocortin-4 receptor agonistic action may offer some therapeutic benefits in leptin-deficient patients.
Learning points:
-
A patient with atypical lipodystrophy with an initial benefit with metreleptin therapy developed neutralizing antibodies to metreleptin (Nab-leptin), which led to substantial worsening in metabolic control. The neutralizing activity in her serum persisted for longer than 3 years.
-
Whether the worsening in her metabolic state was truly caused by the development of Nab-leptin cannot be fully ascertained, but there was a temporal relationship. The experience noted in our patient at least raises the possibility for concern for substantial metabolic worsening upon emergence and persistence of Nab-leptin. Further studies of cases where Nab-leptin is detected and better assay systems to detect and characterize Nab-leptin are needed.
-
The use of setmelanotide, a selective MC4R agonist targeting specific neurons downstream from the leptin receptor activation, was not effective in restoring metabolic control in this complex patient with presumed diminished leptin action due to Nab-leptin.
-
Although stimulating the MC4R pathway was not sufficient to obtain a significant metabolic benefit in lowering triglycerides and helping with her insulin resistance as was noted with metreleptin earlier, there was a mild reduction in reported food intake and appetite.
-
Complex features of our case make it difficult to generalize our observation to all leptin-deficient patients. It is possible that some leptin-deficient patients (especially those who need primarily control of food intake) may still theoretically benefit from MC4R agonistic action, and further studies in carefully selected patients may help to tease out the differential pathways of metabolic regulation by the complex network of leptin signaling system.
Search for other papers by Marcela Rodríguez Flores in
Google Scholar
PubMed
Search for other papers by Ruth Carmina Cruz Soto in
Google Scholar
PubMed
Search for other papers by Verónica Vázquez Velázquez in
Google Scholar
PubMed
Search for other papers by Reina Ruth Soriano Cortés in
Google Scholar
PubMed
Endocrinology and Metabolism Department, Instituto Tecnológico de Estudios Superiores de Monterrey Tec Salud, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Search for other papers by Carlos Aguilar Salinas in
Google Scholar
PubMed
Search for other papers by Eduardo García García in
Google Scholar
PubMed
Summary
In patients with gastric bypass (GB), high glucose variability (GV) and hypoglycemia have been demonstrated, which could impact the metabolic status and eating behavior. We describe the glucose patterns determined through continuous glucose monitoring (CGM) in two patients with >5 years follow-up after GB and significant weight recovery, who reported hypoglycemic symptoms that interfered with daily activities, and their response to a nutritional and psycho-educative prescription. Case 1: A 40-year-old woman without pre-surgical type 2 diabetes (T2DM) and normal HbA1c, in whom CGM showed high GV and hypoglycemic episodes that did not correlate with the time of hypoglycemic symptoms. Her GV reduced after prescription of a diet with low glycemic index and modification of meal patterns. Case 2: A 48-year-old male with pre-surgical diagnosis of T2DM and current normal HbA1c, reported skipping meals. The CGM showed high GV, 15% of time in hypoglycemia and hyperglycemic spikes. After prescription of a low glycemic index diet, his GV increased and time in hypoglycemia decreased. Through the detailed self-monitoring needed for CGM, we discovered severe anxiety symptoms, consumption of simple carbohydrates and lack of meal structure. He was referred for more intensive psychological counseling. In conclusion, CGM can detect disorders in glucose homeostasis derived both from the mechanisms of bariatric surgery, as well as the patient’s behaviors and mental health, improving decision-making during follow-up.
Learning points:
-
High glycemic variability is frequent in patients operated with gastric bypass.
-
Diverse eating patterns, such as prolonged fasting and simple carbohydrate ingestion, and mental health disorders, including anxiety, can promote and be confused with worsened hypoglycemia.
-
CGM requires a detailed record of food ingested that can be accompanied by associated factors (circumstances, eating patterns, emotional symptoms). This allows the detection of particular behaviors and amount of dietary simple carbohydrates to guide recommendations provided within clinical care of these patients.
Search for other papers by Michelle Maher in
Google Scholar
PubMed
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland
Search for other papers by Mohammed Faraz Rafey in
Google Scholar
PubMed
Search for other papers by Helena Griffin in
Google Scholar
PubMed
Search for other papers by Katie Cunningham in
Google Scholar
PubMed
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland
Search for other papers by Francis M Finucane in
Google Scholar
PubMed
Summary
A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team.
Learning points:
-
Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss.
-
Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up.
-
For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option.
-
Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary.
-
In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.
Search for other papers by Xin Chen in
Google Scholar
PubMed
Search for other papers by Dina Kamel in
Google Scholar
PubMed
Search for other papers by Braden Barnett in
Google Scholar
PubMed
Search for other papers by Evan Yung in
Google Scholar
PubMed
Search for other papers by Adrienne Quinn in
Google Scholar
PubMed
Search for other papers by Caroline Nguyen in
Google Scholar
PubMed
Summary
There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH). Histopathologic findings from such patients who underwent partial/total pancreatomy, however, can vary widely from minimal changes to classic nesidioblastosis, making the pathologic diagnosis challenging. PGBH typically presents as postprandial hypoglycemia, as opposed to insulinoma, which presents as fasting hypoglycemia. Herein, we describe an unusual case of a patient with PGBH who initially presented with postprandial hypoglycemia three years after surgery, but later developed fasting hyperinsulinemic hypoglycemia as the disease progressed. Our hypothesis for this phenomenon is that this disease is progressive, and later in its course, the insulin release becomes dissociated from food stimulation and is increased at baseline. Future studies are needed to investigate the prevalence as well as etiology of this progression from postprandial to fasting hypoglycemia.
Learning points:
-
There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH).
-
Histopathologically, PGBH can vary from minimal changes to nesidioblastosis.
-
Although uncommon, patients with PGBH after Roux-en-Y gastric bypass may present with both postprandial and fasting hyperinsulinemic hypoglycemia as disease progresses.
-
Our hypothesis for this phenomenon is that the insulin release becomes dissociated from food stimulation and is increased at baseline with disease progression.