Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test

Kefurt, Ronald; Langer, Felix B.; Schindler, Karin; Shakeri-Leidenmühler, Soheila; Ludvik, Bernhard; Prager, Gerhard

doi:10.1016/j.soard.2014.11.003

Cited by 115 publications

(87 citation statements)

References 49 publications

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“…[8][9][10] CGM for Guiding Diabetes Management CGM systems can be used blinded or open. When we are using CGM short-term to identify trends, such as postprandial glucose peaks, hypoglycemia, and dawn phenomenon, it is often cleaner to use blinded CGM where data are not displayed to the patient and therefore cannot be used to influence the readings.…”

Section: (5) Diagnosismentioning

confidence: 99%

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes

Slattery

Choudhary

2017

Diabetes Technology & Therapeutics

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With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated ''insulin-suspend'' system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle Ò LibreÔ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.

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Section: (5) Diagnosismentioning

confidence: 99%

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes

Slattery

Choudhary

2017

Diabetes Technology & Therapeutics

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“…This disorder leads to frequent episodes of postprandial hypoglycaemia, with glucose concentrations low enough to cause seizures, loss of consciousness, cognitive dysfunction, disability and death. The threat of neuroglycopenia is worsened by a high prevalence of hypoglycaemia unawareness, with one study demonstrating that continuous glucose monitoring over 5 days detected hypoglycaemic episodes of < 3.05 mmol/l in 75% of post-RYGB patients [15]. There are no approved pharmacotherapies and treatment typically rests on dietary changes, including frequent small meals with dietary carbohydrate restriction.…”

Section: Introductionmentioning

confidence: 99%

Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia

et al. 2016

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Aims/hypothesis Post-bariatric hypoglycaemia (PBH) is a rare, but severe, metabolic disorder arising months to years after bariatric surgery. It is characterised by symptomatic postprandial hypoglycaemia, with inappropriately elevated insulin concentrations. The relative contribution of exaggerated incretin hormone signalling to dysregulated insulin secretion and symptomatic hypoglycaemia is a subject of ongoing inquiry. This study was designed to test the hypothesis that PBH and associated symptoms are primarily mediated by glucagon-like peptide-1 (GLP-1). Methods We conducted a double-blinded crossover study wherein eight participants with confirmed PBH were assigned in random order to intravenous infusion of the GLP-1 receptor (GLP-1r) antagonist, exendin (9-39) (Ex-9), or placebo during an OGTT on two separate days at the Stanford University Clinical and Translational Research Unit. Metabolic, symptomatic and pharmacokinetic variables were evaluated. Results were compared with a cohort of BMI- and glucose-matched non-surgical controls (NSCs). Results Infusion of Ex-9 decreased the time to peak glucose and rate of glucose decline during OGTT, and raised the postprandial nadir by over 70%, normalising it relative to NSCs and preventing hypoglycaemia in all PBH participants. Insulin AUC and secretion rate decreased by 57% and 71% respectively, and peak postprandial insulin was normalised relative to NSCs. Autonomic and neuroglycopenic symptoms were significantly reduced during Ex-9 infusion. Conclusions/interpretation GLP-1r blockade prevented hypoglycaemia in 100% of individuals, normalised beta cell function and reversed neuroglycopenic symptoms, supporting the conclusion that GLP-1 plays a primary role in mediating hyperinsulinaemic hypoglycaemia in PBH. Competitive antagonism at the GLP-1r merits consideration as a therapeutic strategy.

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“…One rare but increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) surgery is severe hypoglycemia with neuroglycopenia [4, 5]. While severe hypoglycemia may occur in fewer than 1% of patients [6–8], mild, often unrecognized, hypoglycemia is more frequent [9, 10] and may contribute to increased appetite and weight regain after surgery [11]. More severely affected patients can develop profound neuroglycopenia, with falls, motor vehicle accidents, loss of consciousness, and seizures refractory to dietary management.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass

Patti

Goldfine

et al. 2017

Acta Diabetol

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Aims Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones are implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB+NG). We aimed to determine whether β-cell proliferation or apoptosis are altered in RYGB+NG. Methods We performed an observational study to analyze markers of proliferation, apoptosis, and cell cycle, and transcription factor expression in pancreatic tissue from affected RYGB+NG patients (n=12), normoglycemic patients undergoing pancreatic surgery for benign lesions (controls, n=6, and individuals with hypoglycemia due to insulinoma (n=52). Results Proliferative cell nuclear antigen (PCNA) expression was increased in insulin-positive cells in RYGB+NG patients (4.5-fold increase, p<0.001 vs. controls) and correlated with β-cell mass. Ki-67 immunoreactivity was low in both RYGB+NG and controls, but did not differ between groups. Phospho-histone H3 levels did not differ between RYGB+NG and controls. PCNA and Ki-67 were both significantly lower in both controls and RYGB+NG than insulinomas. Markers of apoptosis and cell cycle (M30, p27, and p21) did not differ between groups. PDX1 and menin exhibited similar expression patterns, while FOXO1 appeared to be more cytosolic in RYGB+NG. Conclusions Markers of proliferation are heterogeneous in patients with severe post-RYGB hypoglycemia. Increased β-cell proliferation in some individuals may contribute to increased β-cell mass observed in severely affected patients.

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Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test

Cited by 115 publications

References 49 publications

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes

Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia

Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass

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