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Philip E. Cryer - One of the best experts on this subject based on the ideXlab platform.
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hypoglycemia in diabetes
Diabetes Care, 2003Co-Authors: Philip E. Cryer, Stephen N Davis, Harry ShamoonAbstract:Iatrogenic hypoglycemia causes recurrent morbidity in most people with type 1 diabetes and many with type 2 diabetes, and it is sometimes fatal. The barrier of hypoglycemia generally precludes maintenance of euglycemia over a lifetime of diabetes and thus precludes full realization of euglycemia’s long-term benefits. While the clinical presentation is often characteristic, particularly for the experienced individual with diabetes, the neurogenic and neuroglycopenic symptoms of hypoglycemia are nonspecific and relatively insensitive; therefore, many episodes are not recognized. Hypoglycemia can result from exogenous or endogenous insulin excess alone. However, iatrogenic hypoglycemia is typically the result of the interplay of absolute or relative insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors that normally prevent or rapidly correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation. Reduced sympathoadrenal responses cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. Thus, short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. The clinical approach to minimizing hypoglycemia while improving glycemic control includes 1 ) addressing the issue, 2 ) applying the principles of aggressive glycemic therapy, including flexible and individualized drug regimens, and 3 ) considering the risk factors for iatrogenic hypoglycemia. The latter include factors that result in absolute or relative insulin excess: drug dose, timing, and type; patterns of food ingestion and exercise; interactions with alcohol and other drugs; and altered sensitivity to or clearance of insulin. They also include factors that are clinical surrogates of compromised glucose counterregulation: endogenous insulin deficiency; history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se, as evidenced by lower HbA 1c levels, lower glycemic goals, or both. In a patient with hypoglycemia unawareness (which implies recurrent hypoglycemia) a 2- to 3-week period of scrupulous avoidance of hypoglycemia is advisable. Pending the prevention and cure of diabetes or the development of methods that provide glucose-regulated insulin replacement or secretion, we need to learn to replace insulin in a much more physiological fashion, to prevent, correct, or compensate for compromised glucose counterregulation, or both if we are to achieve near-euglycemia safely in most people with diabetes.
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hypoglycemia associated autonomic failure in advanced type 2 diabetes
Diabetes, 2002Co-Authors: Scott A Segel, Deanna S Paramore, Philip E. CryerAbstract:We tested the hypotheses that the glucagon response to hypoglycemia is reduced in patients who are approaching the insulin-deficient end of the spectrum of type 2 diabetes and that recent antecedent hypoglycemia shifts the glycemic thresholds for autonomic (including adrenomedullary epinephrine) and symptomatic responses to hypoglycemia to lower plasma glucose concentrations in type 2 diabetes. Hyperinsulinemic stepped hypoglycemic clamps (85, 75, 65, 55, and 45 mg/dl steps) were performed on two consecutive days, with an additional 2 h of hypoglycemia (50 mg/dl) in the afternoon of the first day, in 13 patients with type 2 diabetes---7 treated with oral hypoglycemic agents (OHA R(X); mean [+/- SD] HbA(1c) 8.6 +/- 1.1%) and 6 requiring therapy with insulin for an average of 5 years and with reduced C-peptide levels (insulin R(X), HbA(1c) 7.5 +/- 0.7%)---and 15 nondiabetic control subjects. The glucagon response to hypoglycemia was virtually absent (P = 0.0252) in the insulin-deficient type 2 diabetic patients (insulin R(X) mean [+/- SE] final values of 52 plus minus 16 vs. 93 plus minus 15 pg/ml in control subjects and 98 +/- 16 pg/ml in type 2 diabetic patients, OHA R(X) on day 1). Glucagon (P = 0.0015), epinephrine (P = 0.0002), and norepinephrine (P = 0.0138) responses and neurogenic (P = 0.0149) and neuroglycopenic (P = 0.0015) symptom responses to hypoglycemia were reduced on day 2 after hypoglycemia on day 1 in type 2 diabetic patients; these responses were not eliminated, but their glycemic thresholds were shifted to lower plasma glucose concentrations. In addition, the glycemic thresholds for these responses were at higher-than-normal plasma glucose concentrations (P = 0.0082, 0.0028, 0.0023, and 0.0182, respectively) at baseline (day 1) in OHA R(X) type 2 diabetic patients, with relatively poorly controlled diabetes. Because the glucagon response to falling plasma glucose levels is virtually absent and the glycemic thresholds for autonomic and symptomatic responses to hypoglycemia are shifted to lower glucose concentrations by recent antecedent hypoglycemia, patients with advanced type 2 diabetes, like those with type 1 diabetes, are at risk for hypoglycemia-associated autonomic failure and the resultant vicious cycle of recurrent iatrogenic hypoglycemia.
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SYMPTOMS OF HYPOGLYCEMIA, THRESHOLDS FOR THEIR OCCURRENCE, AND HYPOGLYCEMIA UNAWARENESS
Endocrinology and metabolism clinics of North America, 1999Co-Authors: Philip E. CryerAbstract:Ultimately traceable to neural glucose deprivation, symptoms of hypoglycemia include neurogenic (autonomic) and neuroglycopenic symptoms. Neurogenic symptoms (tremulousness, palpitations, anxiety, sweating, hunger, paresthesias) are the results of the perception of physiologic changes caused by the autonomic nervous system's response to hypoglycemia. Neuroglycopenic symptoms (confusion, sensation of warmth, weakness or fatigue, severe cognitive failure, seizure, coma) are the results of brain glucose deprivation itself. Glycemic thresholds for symptoms of hypoglycemia shift to lower plasma glucose concentrations following recent episodes of hypoglycemia, leading to the syndrome of hypoglycemia unawareness--loss of the warning symptoms of developing hypoglycemia. Thus, patients with recurrent hypoglycemia (e.g., those with tightly controlled diabetes or with an insulinoma) often tolerate abnormally low plasma glucose concentrations without symptoms.
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reversibility of unawareness of hypoglycemia in patients with insulinomas
The New England Journal of Medicine, 1993Co-Authors: Asimina Mitrakou, Carmine G Fanelli, Thiemo Veneman, G Perriello, S Calderone, D Platanisiotis, A M Rambotti, S Raptis, P Brunetti, Philip E. CryerAbstract:Background A lack of appropriate autonomic warning symptoms before the development of Neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon. Methods To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex. Results Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [±SD], 3.5 ±0.8 vs. 9.6 ±4.5) a...
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Induction of Hypoglycemia Unawareness by Asymptomatic Nocturnal Hypoglycemia
Diabetes, 1993Co-Authors: Thiemo Veneman, Philip E. Cryer, Asimina Mitrakou, Marian Mokan, John E. GerichAbstract:Hypoglycemia has been incriminated as a possible factor responsible for development of the hypoglycemia unawareness phenomenon in patients with type I diabetes. Many patients with this condition, however, do not have a history of recent hypoglycemia. Because asymptomatic nocturnal hypoglycemia commonly occurs in type I diabetes, we tested the hypothesis that such episodes might be capable of inducing this phenomenon. Accordingly, autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive function were assessed during standardized insulin-induced hypoglycemia in 10 normal volunteer subjects on two occasions—once after induction of asymptomatic nocturnal hypoglycemia and once after control studies in which saline rather than insulin was infused overnight. Compared with control experiments, asymptomatic nocturnal hypoglycemia increased the threshold (required greater hypoglycemia for initiation) and reduced the magnitude of autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive dysfunction during subsequent hypoglycemia (all, P < 0.05). These results indicate that asymptomatic hypoglycemia may induce hypoglycemia unawareness and, thus, may explain why not every patient with this condition has a history of prior hypoglycemia. Our results therefore support the concept that in type I diabetes this phenomenon may be largely attributable to antecedent hypoglycemia.
Maryelizabeth Patti - One of the best experts on this subject based on the ideXlab platform.
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hypoglycemia after gastric bypass surgery current concepts and controversies
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Marzieh Salehi, Tracey Mclaughlin, Adrian Vella, Maryelizabeth PattiAbstract:Context Hypoglycemia, occurring after bariatric and other forms of upper gastrointestinal surgery, is increasingly encountered by clinical endocrinologists. The true frequency of this condition remains uncertain, due, in part, to differences in the diagnostic criteria and in the affected populations, as well as relative lack of patient and physician awareness and understanding of this condition. Postbariatric hypoglycemia can be severe and disabling for some patients, with Neuroglycopenia (altered cognition, seizures, and loss of consciousness) leading to falls, motor vehicle accidents, and job and income loss. Moreover, repeated episodes of hypoglycemia can result in hypoglycemia unawareness, further impairing safety and requiring the assistance of others to treat hypoglycemia.
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insulin response to oral stimuli and glucose effectiveness increased in Neuroglycopenia following gastric bypass
Obesity, 2015Co-Authors: Maryelizabeth Patti, Allison B GoldfineAbstract:Objective Hyperinsulinemic hypoglycemia with Neuroglycopenia is a rare complication following Roux-en-Y gastric bypass (RYGB) surgery for weight management. Insulin secretion and action in response to oral and intravenous stimuli in persons with and without Neuroglycopenia following RYGB are evaluated in this study. Methods Cross-sectional cohort studies were performed at a single academic institution to assess insulin secretion and action during oral mixed meal tolerance test and intravenous glucose tolerance test (IVGTT). Results Insulin secretion was increased more following oral mixed meal than intravenous glucose in individuals with Neuroglycopenia compared to the asymptomatic group. Reduced insulin clearance did not contribute to higher insulinemia. Glucose effectiveness at zero insulin, estimated during the IVGTT, was also higher in those with Neuroglycopenia. Insulin sensitivity did not differ between groups. Conclusions Increased beta-cell response to oral stimuli and insulin-independent glucose disposal may both contribute to severe hypoglycemia after RYGB.
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continuous glucose monitoring for evaluation of glycemic excursions after gastric bypass
Journal of Obesity, 2011Co-Authors: Florencia Halperin, Maryelizabeth Patti, Megan Skow, Muhammad Bajwa, Allison B GoldfineAbstract:Background. Hyperinsulinemic hypoglycemia with Neuroglycopenia is a rare complication of Roux-en-Y gastric bypass (RYGB). We hypothesized that continuous glucose monitoring (CGM) would be useful to characterize glycemic variability after RYGB. Methods. CGM and mixed meal tolerance testing (MMTT) were performed on sixteen post-RYGB subjects, ten with a history of Neuroglycopenia on medical treatment and six asymptomatic controls. Results. 9 of 10 subjects with Neuroglycopenia developed hypoglycemia defined by glucose <70 mg/dL on CGM, and 3 of 9 on MMTT. In asymptomatic subjects, 3 of 6 had asymptomatic hypoglycemia during CGM, and 3 of 5 on MMTT. Therefore, the sensitivity and specificity to detect clinically significant hypoglycemia was 90% and 50% for CGM and 33% and 40% for MMTT.Conclusions. Asymptomatic hypoglycemia after RYGB is more frequent than commonly recognized. For clinicians evaluating patients for postbypass Neuroglycopenia, CGM may be a valuable diagnostic tool.
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patients with Neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal
The Journal of Clinical Endocrinology and Metabolism, 2007Co-Authors: Allison B Goldfine, Jens J Holst, Edward C Mun, E Devine, Raphael Bernier, M Bazhecht, Daniel B Jones, Benjamin E Schneider, Maryelizabeth PattiAbstract:Context and Objective: Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive -cell function and/or growth. Patients and Methods: We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixedmeal challenge, in four subject groups: 1) with clinically significant hypoglycemia [Neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts. Results: Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagonlike peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients. Conclusion:A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response. (J Clin Endocrinol Metab 92: 4678–4685, 2007)
Bo Ahrén - One of the best experts on this subject based on the ideXlab platform.
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differential impairment of glucagon responses to hypoglycemia Neuroglycopenia arginine and carbachol in alloxan diabetic mice
Metabolism-clinical and Experimental, 2002Co-Authors: Bo Ahrén, Gerald J Taborsky, Peter J HavelAbstract:To gain insight into the mechanisms responsible for the loss of the glucagon response to insulin-induced hypoglycemia in type 1 diabetes, glucagon responses to 4 different stimuli were examined over 3 months of diabetes in alloxan-treated mice. At 1, 6, and 12 weeks after alloxan (60 mg/kg), phloridzin (0.1 g/kg) was administered to overnight fasted diabetic mice to match the glucose levels of those in nondiabetic control mice before administration of the acute stimuli. Despite the elevation of baseline glucagon levels produced by the phloridzin treatment, the glucagon responses to insulin (2 U/kg intraperitoneally [IP])-induced hypoglycemia was not impaired at 1 week. However, the response was reduced by greater than 60% after 6 and 12 weeks of diabetes (P <.05). In contrast, the glucagon response to arginine (0.25 g/kg intravenously [IV]) was not reduced after 1, 6, or 12 weeks of diabetes, ruling out a generalized impairment of the A-cell responses. The glucagon response to the neuroglucopenic agent, 2-deoxyglucose (2-DG; 500 mg/kg IV) was impaired, like that to insulin-induced hypoglycemia, after 6 and 12 weeks of diabetes (P <.05), suggesting that supersensitivity to the potential inhibitory effects of exogenous insulin is not the mechanism responsible for the impairment. Finally, the glucagon response to the cholinergic agonist, carbachol (0.53 micromol/kg IV), was not impaired in the diabetic animals, arguing against a defect in the A-cell's responsiveness to autonomic stimulation. The data suggest that the impairment of the glucagon response to insulin-induced hypoglycemia in alloxan diabetic mice is not due to a generalized impairment of A-cell responsiveness, to desensitization by a suppressive action of insulin, or to impairment of the A-cell response to autonomic stimuli. The remaining mechanisms which are likely to explain the late loss of the glucagon response to insulin-induced hypoglycemia include (1) a defect in the A-cell recognition of glucopenic stimuli, or (2) a defect in the autonomic inputs to the A cell that are known to be activated by glucopenic stimuli.
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autonomic regulation of islet hormone secretion implications for health and disease
Diabetologia, 2000Co-Authors: Bo AhrénAbstract:The pancreatic islets are richly innervated by parasympathetic, sympathetic and sensory nerves. Several different neurotransmitters are stored within the terminals of these nerves, both the classical neurotransmitters, acetylcholine and noradrenaline, and several neuropeptides. The neuropeptides, vasoactive intestinal polypeptide, pituitary adenlyate cyclase activating polypeptide and gastrin releasing peptide are constituents of the parasympathetic nerves, whereas the neuropeptides galanin and neuropeptide Y are localised to sympathetic nerve terminals. Furthermore, the neuropeptide calcitonin gene-related peptide is localised to sensory nerves and cholecystokinin is also an islet neuropeptide, although the nature of the cholecystokinin nerves is not established. Stimulation of the autonomic nerves and treatment with neurotransmitters affect islet hormone secretion. Thus, insulin secretion is stimulated by parasympathetic nerves or their neurotransmitters and inhibited by sympathetic nerves or their neurotransmitters. The islet autonomic nerves seem to be of physiological importance in mediating the cephalic phase of insulin secretion, in synchronising the islets to function as a unit allowing oscillations of islet hormone secretion, and in optimising islet hormone secretion during metabolic stress, e. g. hypoglycaemia and Neuroglycopenia. The autonomic nerves could also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and Type II (non-insulin-dependent) diabetes mellitus. It is concluded that islet innervation, through the contribution of all branches of the autonomic nerves and several different neurotransmitters is of importance both for the physiology and pathophysiology of the islets. [Diabetologia (2000) 43: 393–410]
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stimulation of endocrine but not exocrine pancreatic secretion during 2 deoxy d glucose induced Neuroglycopenia in the conscious pig
Pancreas, 1995Co-Authors: Sven Karlsson, Bo Ahrén, Stefan Pierzynowski, Bjorn Westrom, Maryjane Thaela, Borje W KarlssonAbstract:The effects of autonomic nervous activation, initiated by 2-deoxy-D-glucose (2-DG)-induced Neuroglycopenia, on endocrine and exocrine pancreatic secretion were investigated in the conscious pig. Pigs were surgically fitted with permanent pancreatic duct and duodenal reentrant cannulas, allowing long-term sampling of pancreatic juice, and a jugular vein catheter for blood sampling and infusion of 2-DG. 2-DG was administered as a 5-min intravenous infusion at three dose levels to conscious pigs. 2-DG (400 mg/kg) was found to elevate plasma glucagon and insulin levels (p < 0.01). In contrast, exocrine pancreatic secretion, measured as volume, total protein output, and output of trypsin activity was not affected by 2-DG at the dose levels of 75, 200, and 400 mg/kg. Secretin (440 pmol/kg/h), however, stimulated pancreatic exocrine output of fluid (p < 0.01), protein (p < 0.01), and trypsin (p < 0.05). It is concluded that autonomic nervous activation by 2-DG-induced Neuroglycopenia, in the conscious pig under basal conditions, elevates the plasma levels of glucagon and insulin but does not affect exocrine pancreatic secretion. 2-DG-induced Neuroglycopenia is, thus, a suitable model for studying autonomic neural influences on the porcine endocrine pancreas.
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involvement of nitric oxide in Neuroglycopenia induced insulin and glucagon secretion in the mouse
European Journal of Pharmacology, 1995Co-Authors: Bo Ahrén, Sven Karlsson, Anton J W Scheurink, A B SteffensAbstract:Abstract Neuroglycopenia induced by administration of 2-deoxy- d -glucose is known to stimulate the secretion of both insulin and glucagon in mice by a mechanism that is dependent on neural activity. In the present study, we examined whether the neurotransmitter nitric oxide (NO) is involved in this process. Therefore, 2-deoxy- d -glucose (500 mg/kg) was injected intravenously alone or together with the inhibitor of NO synthase, NG-nitro- l -arginine methyl ester (50 mg/kg) to conscious mice. It was found that NG-nitro- l -arginine methyl ester inhibited the increased plasma levels of both insulin (by 26%; P = 0.039) and glucagon (by 45%; P d -glucose. Similarly, the NO synthase inhibitor, NG-nitro- l -arginine, which is devoid of the anticholinergic property of NG-nitro- l -arginine methyl ester, inhibited the responses of both insulin (by 53%; P = 0.026) and glucagon (by 57%; P = 0.003) to 2-deoxy- d -glucose. In contrast, the stereoisomer of NG-nitro- l -arginine methyl ester, NG-nitro- d -arginine methyl ester, which is devoid of NO synthase inhibitory activity, was without effect on 2-deoxy- d -glucose-induced insulin and glucagon secretion. Plasma levels of adrenaline and noradrenaline after administration of 2-deoxy- d -glucose were also reduced by NG-nitro- l -arginine methyl ester. In contrast, the insulin and glucagon secretory responses to intravenous injection of arginine (250 mg/kg), glucose (500 mg/kg) or the cholinergic agonist, carbachol (30 μg/kg), were not influenced by NG-nitro- l -arginine methyl ester, NG-nitro- d -arginine methyl ester or NG-nitro- l -arginine. We conclude that the increased secretion of both insulin and glucagon during Neuroglycopenia in the mouse is partially mediated by NO.
Tracey Mclaughlin - One of the best experts on this subject based on the ideXlab platform.
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hypoglycemia after gastric bypass surgery current concepts and controversies
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Marzieh Salehi, Tracey Mclaughlin, Adrian Vella, Maryelizabeth PattiAbstract:Context Hypoglycemia, occurring after bariatric and other forms of upper gastrointestinal surgery, is increasingly encountered by clinical endocrinologists. The true frequency of this condition remains uncertain, due, in part, to differences in the diagnostic criteria and in the affected populations, as well as relative lack of patient and physician awareness and understanding of this condition. Postbariatric hypoglycemia can be severe and disabling for some patients, with Neuroglycopenia (altered cognition, seizures, and loss of consciousness) leading to falls, motor vehicle accidents, and job and income loss. Moreover, repeated episodes of hypoglycemia can result in hypoglycemia unawareness, further impairing safety and requiring the assistance of others to treat hypoglycemia.
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reversible hyperinsulinemic hypoglycemia after gastric bypass a consequence of altered nutrient delivery
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Tracey Mclaughlin, Marcia C Peck, Jens J Holst, Carolyn F DeaconAbstract:Context: Severe hypoglycemia after Roux-en-Y gastric bypass surgery (RYGB) is an increasingly recognized condition, characterized by Neuroglycopenia and inappropriately elevated insulin concentrations that occur primarily in the postprandial state. Both pathophysiology and treatment of this disorder remain elusive, but it has been postulated that hyperplasia and/or hypertrophy of β-cells due to morbid obesity and/or postsurgical nesidioblastosis may contribute. Objective: The objective of this study was to elucidate the pathophysiology of this condition; specifically, we hypothesized that metabolic abnormalities were a function of altered nutrient transit through the gastrointestinal tract rather than anatomical changes to pancreatic β-cells that would lead to consistently high insulin secretion irrespective of nutrient transit route. Design/Setting/Subject/Outcome Measures: We describe a unique case wherein gastrostomy tube (GT) insertion into the remnant stomach reversed neuroglycopenic symptoms. This s...
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plasma glucose and insulin regulation is abnormal following gastric bypass surgery with or without Neuroglycopenia
Obesity Surgery, 2009Co-Authors: Sun H Kim, Teresa C Liu, Fahim Abbasi, Cindy Lamendola, John M Morton, Gerald M Reaven, Tracey MclaughlinAbstract:Enhanced insulin sensitivity is commonly seen following Roux-en-Y gastric bypass surgery (RYGB) whereas symptomatic hypoglycemia post-RYGB seems to occur infrequently. It is unclear how different plasma glucose and insulin responses are in patients with symptomatic hypoglycemia (SX-RYGB) versus those who remain asymptomatic (ASX-RYGB), nor when compared with non-surgical controls with varying degrees of insulin sensitivity. Plasma glucose and insulin concentrations were determined following a 75-g oral glucose challenge in five groups: symptomatic and asymptomatic patients following RYGB (n = 9 each) and overweight/obese controls, divided into three subgroups (n = 30 each) on the basis of degree of insulin sensitivity measured by the insulin suppression test. SX-RYGB group had higher 30-min glucose after oral glucose compared with the ASX-RYGB group (p = 0.04). The two groups did not differ in peak glucose and insulin concentrations, nadir glucose concentration, or insulin-to-glucose ratio 30 min after oral glucose. These values were significantly different from the three control groups, and peak insulin concentrations post-RYGB were increased at every degree of insulin sensitivity as compared with the control groups. Plasma glucose and insulin responses to oral glucose in patients with symptomatic hypoglycemia post-RYGB are minimally different when compared to individuals who remain asymptomatic, and both groups demonstrate hyperinsulinemia out of proportion to their degree of insulin sensitivity.
Ricardo V Lloyd - One of the best experts on this subject based on the ideXlab platform.
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hyperinsulinemic hypoglycemia with nesidioblastosis after gastric bypass surgery
The New England Journal of Medicine, 2005Co-Authors: Geoffrey B Thompson, James C Andrews, Maria L Collazoclavell, Ricardo V LloydAbstract:We describe six patients (five women and one man; median age, 47 years; range, 39 to 54) with postprandial symptoms of Neuroglycopenia owing to endogenous hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass surgery. Except for equivocal evidence in one patient, there was no radiologic evidence of insulinoma. Selective arterial calcium-stimulation tests, positive in each patient, were used to guide partial pancreatectomy. Nesidioblastosis was identified in resected specimens from each patient, and multiple insulinomas were identified in one. Hypoglycemic symptoms diminished postoperatively. We speculate that hyperfunction of pancreatic islets did not lead to obesity but that beta-cell trophic factors may have increased as a result of gastric bypass.
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noninsulinoma pancreatogenous hypoglycemia a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in kir6 2 and sur1 genes
The Journal of Clinical Endocrinology and Metabolism, 1999Co-Authors: Neena Natt, Geoffrey B Thompson, James C Andrews, Clive S Grant, Jonathan A Van Heerden, Eva Lorenz, Andre Terzic, Ricardo V LloydAbstract:In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic β-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium ...