Hypoglycemia (Reactive Hypoglycemia)

A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.

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Networked: 13816 relevant articles (679 outcomes, 1387 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Weight Gain
2.	Hyperglycemia
3.	Weight Loss (Weight Reduction)
4.	Body Weight (Weight, Body)
5.	Insulinoma

Experts

1.	Davis, Stephen N: 42 articles (09/2015 - 05/2002)
2.	Sherwin, Robert S: 36 articles (09/2015 - 03/2002)
3.	Cryer, Philip E: 36 articles (07/2014 - 03/2002)
4.	Hussain, Khalid: 32 articles (12/2015 - 11/2003)
5.	Rosenstock, Julio: 31 articles (09/2015 - 11/2003)
6.	Tamborlane, William V: 29 articles (09/2015 - 05/2002)
7.	Kollman, Craig: 27 articles (11/2015 - 06/2004)
8.	Stanley, Charles A: 26 articles (11/2015 - 12/2002)
9.	Briski, Karen P: 26 articles (02/2015 - 12/2005)
10.	Umpierrez, Guillermo E: 25 articles (12/2015 - 09/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Hypoglycemia:

1.	Insulin (Novolin)FDA Link 04/01/2015 - "The most basic form of automation, suspension of insulin delivery for actual or predicted hypoglycemia, has been shown to be effective and well tolerated, and a first-generation device has actually reached the market. " 03/01/2015 - "The insulin application method most recommended consisting in a basal-bolus regimen which has shown efficacy with a low risk of hypoglycemia. " 09/01/2010 - "These algorithms modulate the insulin pump delivery so that the insulin injection rate is dramatically reduced when the risk of hypoglycemia is high. " 10/01/1999 - "The insulin hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. " 06/01/1999 - "Provocation tests are most commonly used for the diagnosis with the insulin-induced hypoglycemia test nowadays considered as the "gold standard". "
2.	Glucose (Dextrose)FDA LinkGeneric 05/01/2015 - "Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. " 05/01/2008 - "The protocol was highly effective in normalizing glucose without hypoglycemia. " 08/01/2004 - "For most, improvement in glucose control with resolution of glycemic lability and hypoglycemia has been a net benefit." 11/01/2002 - "There was a 2-fold increase (45% vs 22%, P =.015) in the incidence of hypoglycemia with a bedtime glucose </=100 mg/dL and a 1.7-fold increase (46% vs 26%, P =.01) with a value of </=150 mg/dL; most episodes occurred between 9 PM and 1 AM. There was no difference in hypoglycemia duration (86.4 minutes for glucose </=100 mg/dL vs 84.5 minutes for >100 mg/dL, P = NS), and no bedtime glucose value between 110 and 300 mg/dL decreased the incidence of nocturnal hypoglycemia to </=10%. " 07/01/2014 - "Since increased risk of hypoglycemia appears to be the major obstacle of tight glucose control, we try to put forward novel approaches that may help to achieve optimal glucose control with low risk of hypoglycemia. "
3.	Blood Glucose (Blood Sugar)IBA 01/01/2004 - "Newer insulins and easier blood glucose monitoring have greatly improved the ability to obtain excellent control of blood glucose levels with less risk of hypoglycemia. " 01/01/2008 - "To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. " 10/09/2012 - "GA may also reflect the status of blood glucose more rapidly (2-3 weeks) than HbA1c (2-3 months), and is beneficial in those with wide variations in blood glucose or at higher risk for hypoglycemia. " 11/01/2009 - "Although glycemic control was significantly improved, the patient safety risk from hypoglycemia did not increase, as rates of blood glucose <50 mg/dL decreased from 0.68% at baseline to 0.64% in 2007." 10/01/2009 - "Significant differences were observed with respect to HbA(1c) (P<0.05), well-being (P<0.05), diabetes-related distress (P<0.01), frequency of blood glucose testing (P<0.05), avoidance of hypoglycemia (P<0.01), perceived stress (P<0.05), anxiety (P<0.05) and depression (P<0.05), all of which showed greater improvement in the intervention group compared with the control group. "
4.	Glucagon (Glukagon)FDA Link 10/01/2002 - "Glucagon infusions appear to be beneficial for problematic neonatal hypoglycemia of different causes." 01/01/1992 - "During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). " 11/01/2014 - "Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. " 09/01/2012 - "Glucagon seemed mostly effective in preventing hypoglycemia. " 04/01/1991 - "Glucagon is safe and effective therapy for hypoglycemia in the prehospital setting."
5.	glargine (insulin glargine)FDA Link 01/01/2011 - "the AT-LANTUS Study demonstrated that a simple subject-administered titration algorithm significantly improved glycemic control with a low incidence of severe hypoglycemia compared with a physician-managed titration. " 05/01/2014 - "Reductions in HbA1c level and hypoglycemia rates were significantly greater with glargine use than with intensification of OADs or lifestyle modifications, overall, and in patients with any CVRF. " 06/01/2013 - "Insulin glargine was associated with better glycemic control and a reduced incidence of daytime and any hypoglycemia versus comparator interventions in both younger and older T2DM patients. " 05/01/2005 - "The use of FMDI therapy with glargine among preschool-aged children with type 1 DM was associated with improved overall glycemic control and decreased frequency of severe hypoglycemia. " 12/01/2013 - "Based on reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of degludec is likely to be cost-effective compared to glargine from a societal perspective in T1D, T2-BOT, and T2-BB in Sweden over a 1-year time horizon."
6.	Epinephrine (Adrenaline)FDA LinkGeneric 01/01/1998 - "Males had a significantly greater increase in epinephrine release than females exposed to the same pattern of hypoglycemia. " 07/01/1997 - "Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). " 02/01/2000 - "Recent studies indicate that endogenous epinephrine provides protection against hypoglycemia in fasted elderly patients with type 2 diabetes treated with sulfonylureas. " 04/01/2006 - "Protection against epinephrine defects, both without and with antecedent hypoglycemia, is associated with enhancement of adrenal catecholamine-synthesizing enzyme levels." 02/01/1997 - "Recently, the avoidance of clinical hypoglycemia has been reported to improve epinephrine and symptom responses to hypoglycemia in type I patients. "
7.	Hemoglobins (Hemoglobin)IBA 10/01/2007 - "It is still difficult to state with certainty that CGMs allow effective improvement in glycemic control for the majority of patients with type 1 diabetes, in view of the paucity of controlled studies showing an impact on hemoglobin A1c or frequency of hypoglycemia, even if such a tendency seems to emerge from most non-controlled intervention trials. " 08/01/2006 - "Conflicting data have accumulated on the consistency of improvement in hemoglobin A1c (HbA1c) and in the frequency of complications, most significantly that of hypoglycemia. " 08/01/2010 - "Improved metabolic control with significant lowering of glycated hemoglobin (A1C) along with other parameters of glycemia, and without a concomitant increase in hypoglycemia, has been demonstrated. " 11/01/2015 - "Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from -0.5 to -0.8%, without any significant hypoglycemia. " 08/01/2015 - "We studied the effects of TS on nocturnal hypoglycemia (NH) in relation to baseline hemoglobin A1c (A1C) and change in A1C during the study. "
8.	Glucagon-Like Peptide 1 (GLP 1)IBA 07/01/2012 - "The GLP-1 analogues are unique agents which are effective in providing glycemic reduction with a very low risk of hypoglycemia and hence find an important place in the management of diabetes during Ramadan. " 09/01/2003 - "Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. " 01/01/2005 - "Recent studies investigating improved GLP-1 activity have yielded promising results, with improved glycemic control in elderly patients with type 2 diabetes and without significant risk for hypoglycemia. " 01/01/2015 - "GLP-1 plasmatic concentration was decreased, with the PD suggesting to be more beneficial for the athletes in order to avoid hypoglycemia. " 08/15/2014 - "Clinical trials confirm that DPP-4i raises GLP-1 levels in plasma and improves glycemia with very low risk for hypoglycemia and other side effects. "
9.	Hydrocortisone (Cortisol)FDA LinkGeneric 11/01/1992 - "However, the cortisol response to hypoglycemia during DST + hCRH + ITT was significantly greater than during DST+ITT (P < 0.05) and was similar to the cITT response. " 01/01/2014 - " primary aim of this study was to test the associations between midnight salivary cortisol (MSC), depression and HbA1c, and control for behavioural, environmental and intra individual factors with possible impact on cortisol secretion, like smoking, physical inactivity, season, medication, diabetes duration, severe hypoglycemia episodes, age and gender in patients with type 1 diabetes. " 07/15/1997 - "The aim of this study was to determine whether preventing increases in plasma cortisol during antecedent hypoglycemia preserves autonomic nervous system counterregulatory responses during subsequent hypoglycemia. " 08/01/1996 - "The aim of this study was to determine the role of increased plasma cortisol levels in the pathogenesis of hypoglycemia-associated autonomic failure. " 07/01/1989 - "To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. "
10.	NPH InsulinFDA Link 01/01/2007 - "Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH) insulin, with a tendency toward causing less hypoglycemia. " 10/01/2015 - "Rates of LGA, macrosomia, and neonatal hypoglycemia were similar after pregnant women were treated with detemir and NPH insulin. " 08/01/2015 - "However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. " 06/01/2014 - "However, an argument against use of analog insulins as compared with use of regular or NPH insulin is one that states that the effectiveness and risk of hypoglycemia are the only two valid clinical outcomes that should be used to compare the analog and human insulins. " 06/01/2014 - "However, an argument against use of analog insulins as compared with use of regular or NPH insulin is one that states that the effectiveness and risk of hypoglycemia are the only two valid clinical outcomes that should be used to compare the analog and human insulins. "

Therapies and Procedures

1.	Injections 10/01/2001 - "Compared with maximum-dose GB, twice-daily injections of Mix25 resulted in improved glycemic control and treatment satisfaction, and were associated with a predictably higher rate of hypoglycemia in this group of patients with type 2 diabetes who were inadequately controlled with maximum-dose GB. " 04/01/2004 - "Utilization of CSII in several studies has shown reductions in hypoglycemia and improvement in glycemic control compared with multiple daily injections. " 11/01/2012 - "IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy." 10/01/2011 - "However, difficulty in medication administration with multiple daily injections, potential for hypoglycemia, and increase in appetite and weight make this therapeutic option cumbersome for many pregnant patients. " 05/01/2011 - "Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance. "
2.	Islets of Langerhans Transplantation 03/01/2007 - "The objective of the study was to determine whether the avoidance of hypoglycemia achieved through islet transplantation results in improved glycemic thresholds for counterregulatory responses. " 09/01/2015 - "In a large cohort with a 5-year follow-up and in a multicenter network setting, islet transplantation was safe and efficient in restoring good and lasting glycemic control and preventing severe hypoglycemia in patients with type 1 diabetes." 07/01/2015 - "Reversal of Hypoglycemia Unawareness with a Single-donor, Marginal Dose Allogeneic Islet Transplantation in Korea: A Case Report." 10/01/2014 - "Islet transplantation is an effective means of treating severe type 1 diabetes in patients with life-threatening hypoglycemia. " 04/01/2014 - "While islet transplantation is currently generally reserved for adults with type 1 diabetes with severe hypoglycemia or glycemic lability, we herein consider the possibility of its application to the pediatric population."
3.	Pancreatectomy 09/01/2006 - "A second patient had profound hyperinsulinemic hypoglycemia and was treated successfully with a subtotal (95%) pancreatectomy. " 07/01/2003 - "However, no studies assessing the impact of hemi-pancreatectomy in humans on islet alpha-cell responses to hypoglycemia have been reported. " 11/01/2015 - "Pancreatectomy increases the risk for diabetes, whereas recurrent hypoglycemia places children at risk of neurocognitive dysfunction. " 07/01/2013 - "Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is rare, but an important cause of hypoglycemia in infants, associated with a number of structural abnormalities of the endocrine pancreas is collectively termed as "Islet cell dysmaturation syndrome." We present the anesthetic management in a clinically diagnosed case of PHHI in a 22 days old full term child, undergoing Subtotal Pancreatectomy. " 07/01/2013 - "Brittle diabetes (frequent hypoglycemia and labile glycemic control) is common after pancreatectomy. "
4.	Transplantation (Transplant Recipients) 01/01/2003 - "In a health technology assessment from Alberta, Guo et al. (2003) stated that limited evidence from the Edmonton series suggested that islet cell transplantation (ITA) (using the Edmonton Protocol) is effective in 1) controlling labile diabetes and 2) protecting against unrecognized hypoglycemia in highly selected patients in the short term. " 10/01/2015 - "This long-term cohort with more than 7 years of follow-up shows that glycemic control in patients with T1D after SIK/IAK transplantation improved, and the rate of severe hypoglycemia decreased significantly as compared to control groups. " 06/27/2005 - "The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). " 10/01/2006 - "Recent trials are showing that improved glycemic metabolic control, prevention of severe hypoglycemia, and better quality of life can be reproducibly achieved after transplantation of allogeneic islets in patients with unstable T1DM. " 07/01/2014 - "Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. "
5.	Transplants (Transplant) 09/15/2007 - "Prior to transplant, islet recipients had more fear of hypoglycemia than controls (P<0.000001), but this improved up to 36 months after transplant (P<0.00001, pretransplant vs. each time point). " 11/01/2008 - "The improved metabolic control achieved with ITx can restore hypoglycemia awareness in patients with type 1 diabetes, persisting even after islet graft failure." 06/01/2015 - "This algorithm provides an evidence-informed approach to resolving problematic hypoglycemia; it should be used as a guide, with individual patient circumstances directing suitability and acceptability to ensure the prudent use of technology and scarce transplant resources. " 06/01/2015 - "For patients whose problematic hypoglycemia persists, islet or pancreas transplant should be considered (stage 4). " 01/01/2015 - "All patients show persistent graft function, stable glycemic control with a reduction in HbA1c in the absence of hypoglycemia. "