Background: Hypoglycemia is a commonly encountered metabolic state in the patient population. It can be medically defined as a blood sugar <70mg/dL in a diabetic patient or <50mg/dL in a non-diabetic patient. It is less frequently seen in non-diabetics due to the body’s ability to autoregulate insulin administration. Common symptoms are sweating, tremors, palpitations, dizziness, drowsiness, and confusion. If left untreated, these symptoms can progress to seizures, arrythmias, or other complications that ultimately lead to death. Objective: To highlight the possible causes of hypoglycemia and the appropriate work-up for normally euglycemic patients. Case Description: We herein report a case of hypoglycemia in a 36-year-old female with Lupus related end-stage renal disease on hemodialysis via Ash-catheter who presented with peritonitis due to a defunct peritoneal dialysis catheter. The patient was found to be bacteremic; therefore both catheters were removed and antibiotics were started. Repeat blood cultures showed no growth for 48 hours, so the patient was held fasting at midnight for placement of a new catheter. On the day of surgery, she registered multiple blood sugar readings as low as 15mg/dL. Her symptoms were limited to drowsiness and shortness of breath. She was given four D50 boluses, glucagon IV, and a D5 drip that was adjusted to a D15 drip to stabilize her blood sugar. It was discovered that at an admission two months ago, the patient had a few readings in the 30s. She denied any recollection of this and claimed to have been asymptomatic. She also denied a history of low blood sugars and a diagnosis of diabetes. In surgery that day, the patient went into cardiac arrest on the operating table after being sedated. She was resuscitated after one round of chest compressions, and her catheter was placed. During the episodes of low blood sugar, specific labs were drawn for the work-up of hypoglycemia (glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, insulin antibodies, and sulfonylurea/meglitinide screen), but results yielded inconclusive values that prevented a diagnosis. The patient’s blood sugars became steady once her diet was restarted, and she was discharged in stable condition to a rehab facility after cautionary counseling was given. Discussion: This case highlights an optimal way to work-up a patient with new onset hypoglycemia, focusing on patient history and drawing the appropriate labs during hypoglycemic episodes. The specific labs listed above can be used to differentiate between various causes of hypoglycemia (exogenous insulin administration, an insulin secreting tumor [insulinoma], insulin antibodies, insufficient cortisol or glucagon levels, or improper sulfonylurea/meglitinide use) by comparing them to standards. If labs are unable to be obtained, a 72-Hour Fast can be conducted to create a controlled environment, and a Glucagon Tolerance Test can further explore if the cause of hypoglycemia is insulin related. The goal of all of this testing is to be able to identify and treat the underlying cause of the hypoglycemia and prevent future episodes and the complications that accompany it.

Abnormal regulation of growth hormone (GH) secretion has been reported in some patients with insulin-dependent diabetes (IDD). We compared the GH responses in 32 healthy subjects (age 25 ± 2 SE years) and in 23 IDD patients (28 ± 1.9 years old, diabetes duration 10.4 ± 2 years, and glycohemoglobin levels 9.3 ± 2.0%). During acute, severe hypoglycemia (glucose < 40 mg/dl), the mean GH levels were similar. When prolonged mild hypoglycemia was induced (58.0 ± 2.0 mg/dl in the controls and 54.0 ± 2.0 mg/dl in the IDD patients), the mean GH levels were similar, although the increase in GH was delayed in the latter group. During brief (30 min) exercise at 40-50% of VO2 max, GH rose comparably in both groups (IDD patients maintained euglycemia with basal insulin infusion). However, with more prolonged and intense exercise using a glucose clamp to maintain euglycemia, GH rose to 5.4 ± 2.2 ng/ml in controls and 26.4 ± 12.6 ng/ml in the diabetics (P < 0.05). When the combination of intense exercise and hypoglycemia (~ 55 mg/dl) was used, GH rose to a peak of 21.7 ± 2.7 ng/ml in the controls and to 33 ± 3.0 ng/ml in the diabetics (P = NS). Our data show that in insulin-infused IDD patients made euglycemic for these experiments: a) The GH response to acute, severe hypoglycemia was identical to that in the controls and the response to mild, prolonged hypoglycemia was delayed, but of similar magnitude compared with controls; b) Exercise-induced GH responses were observed in both groups, but exaggerated in the diabetics at a higher exercise intensity; c) Hypoglycemia during exercise produced an additive effect on GH secretion in the controls but not in the IDD patients. We conclude that the wide range of abnormal GH secretory responses in type I diabetes reflects a central, possibly hypothalamic, defect in GH regulation.

Hypoglycemia is one of the most serious acute complications in intensively treated diabetes. Recurrent hypoglycemia predisposes individuals to subsequent hypoglycemia, and diminished counterregulatory hormone responses increase this threat. Elevated pancreatic and/or circulating somatostatin has been reported in diabetic humans and animals, and we postulated that excessive somatostatin contributes to the attenuation of counterregulatory hormone release during hypoglycemia in diabetes. It is known that somatostatin suppresses stimulated secretion of glucagon, epinephrine, and corticosterone. We hypothesized that selective somatostatin receptor type 2 (SSTR2) antagonism would: (Study 1) improve hormone counterregulation to hypoglycemia, and (Study 2) ameliorate hypoglycemia in recurrently hypoglycemic rats. Using both high (10 U/kg) and low (5 U/kg) dose insulin to induce hypoglycemia, we demonstrate that inhibiting the action of somatostatin on SSTR2 normalizes the severely attenuated glucagon and corticosterone responses to acute hypoglycemia in diabetic rats. These improvements were specific to diabetes since SSTR2 antagonism did not increase these hormones in non-diabetic rats in response to hypoglycemia. In the absence of hypoglycemia, SSTR2 antagonist neither markedly alters glycemia nor causes sustained elevations in counterregulatory hormones in diabetic animals. Diabetic rats exhibit up to 65% and 75% more pancreatic and plasma somatostatin than non-diabetic rats following hypoglycemia, respectively. Despite improvements of glucagon and corticosterone, expression of gluconeogenic enzymes PEPCK1 and G6Pase was unaltered. SSTR2 antagonism reduced the glucose requirement during a hypoglycemic clamp induced with a lower dose of insulin. In recurrently hypoglycemic diabetic rats, we demonstrate that SSTR2 antagonist treatment reduces the depth and duration of hypoglycemia and promotes the recovery to euglycemia, without affecting the glycemia-lowering effect of insulin. This amelioration of hypoglycemia by SSTR2 antagonism may be attributable in part to the observed modest improvements of glucagon, epinephrine, and corticosterone counterregulation following recurrent hypoglycemia. These results implicate an important role for increased pancreatic, and possibly circulating, somatostatin in defective hypoglycemic counterregulation in diabetes.

[Truncated abstract] Type 1 Diabetes is emerging as a significant public health problem faced by nearly every country in the world. It has major economic and social implications with considerable burden of illness. Approximately 140,000 Australians have been diagnosed with T1DM with an annual increase in incidence rate of 3% per year, comparable to the overall global increase. The management of T1DM requires insulin therapy which places considerable burden on the patient and their carers. Coping with daily insulin injections, dietary changes, modification of physical activity and vigilant monitoring of blood glucose levels, will impact on patient?s quality of life. The optimum goal for the treatment of type 1 diabetes is to safely achieve near-normal glycaemia and failure to maintain this goal accelerates the progression of the devastating long term complications of diabetes. Unfortunately attempts to achieve near normal glycaemia are limited by the risk of excessive lowering of blood glucose levels and hypoglycaemia remains a major barrier to strict glucose control of diabetes. In general this thesis focuses on two fundamental issues related to the epidemiology of severe hypoglycaemia. Namely, methodological consideration when analysing prospective observational data and application of the most robust methodology. A prospective open cohort study of the Princess Margaret Hospital diabetes clinic established in 1992, with 99% case ascertainment was used. This hospital is the only paediatric referral centre for type 1 diabetes and every child diagnosed in the state of Western Australia is treated at this centre. ... The results of this study showed that severe hypoglycaemia remains a major problem and recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycaemia. The study in chapter 7 investigates genetic risk factors related to severe hypoglycaemia. A significant relationship where the presence of the iv deletion (D) allele of the angiotensin-converting enzyme (ACE) increases risk of severe hypoglycaemia has been reported. This study concludes that the presence of D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia. In an attempt to optimize glycemic control, patients may suffer multiple episodes of severe hypoglycaemia which can adversely affect quality of life as well as educational and intellectual disadvantage. The study in chapter 8 investigates the factors related to recurrent severe hypoglycaemia. A rigorous and informative time-to-event approach is used to account for within child correlation, staggered enrolment and timevarying covariates. This allows important risk factors to change over time. Preschool children have an increased risk of experiencing recurrent severe hypoglycaemia. The findings of this thesis highlights the importance of selecting appropriate analytical methodology to identify risk factors associated with severe hypoglycaemia and also to dismiss factors that had previously been thought to be important. This will help in formulating management plans in order to limit the impact of severe hypoglycaemia.

Att som ambulanssjuksköterska behandla patienter med hypoglykemi i hemmet är en vanlig åtgärd, i relation till den ökade belastningen på akutmottagningarna är det viktigt att kunna identifiera vilka patienter som behöver transporteras in till sjukhus. De flesta av patienterna vill stanna kvar i hemmet efter behandling, att vara medveten om vilka potentiella risker som finns om patienten stannar kvar hemma kan göra att det är lättare att bedöma vilken patient som bör åka med till sjukhus. Syftet med denna studie är att belysa riskerna med att patienter som behandlas för hypoglykemi kvarstannar i hemmet.  Studien genomfördes i form av en litteraturstudie. Sökningar gjordes i databaserna PubMed samt Cinahl. Dessa sökningar resulterade i fyra artiklar som inkluderades i resultatet. Under analysen av artiklarna framkom två problemområden, risk för återkommande hypoglykemi samt bristande uppföljning. För att kunna identifiera de patienterna som har ökad risk för återkommande hypoglykemi krävs en adekvat bedömning av sjuksköterskan samt att det finns beslutsstöd till hjälp. Bristande uppföljning av patienterna är det andra problemområdet, där krävs ett förbättrat samarbete mellan ambulans, sjukhus samt primärvård för att kunna förbättra uppföljningen, analysen visade på att även om risken för återkommande hypoglykemi inom 48 timmar är låg, så har många av patienterna upprepade hypoglykemi episoder sett ur ett längre perspektiv vilket understryker vikten av uppföljning. Där kan ambulanssjuksköterskan vara den som initierar uppföljningen, det är dock viktigt att beslutet tas i samråd med patienten. / That as an ambulance nurse treating patients with hypoglycemia in the home is a common practice, in relation to the increased burden on emergency departments, it is important to identify which patients need to be transported to the hospital. Most patients want to stay at home after treatment, to be aware of the potential risks that exist if the patient stays at home can make it easier to determine which patient should go to the hospital. The purpose of this study is to highlight the risks of patients being treated for hypoglycemia remains in the home.  The study was conducted in the form of a literature review. Searches were made in the PubMed and Cinahl. These searches resulted in four articles that were included in the results. During the analysis of the articles revealed two problem areas, the risk of recurrent hypoglycemia and inadequate follow-up. In order to identify those patients who are at increased risk for recurrent hypoglycemia requires an adequate assessment of the nurse and that there are decision supportto help. Lack of follow-up of patients is the second problem area, which require improved cooperation between ambulance, hospital and primary care to improve monitoring, analysis showed that although the risk of recurrent hypoglycemia within 48 hours is low, so many of the patients repeated hypoglycemic episodes from a longer perspective, which emphasizes the importance of follow-up. There, ambulance nurse to be the initiating follow-up, it is important that the decision taken in consultation with the patient.

Thesis (M.S.)--University of Akron, Dept. of Biomedical Engineering, 2008. / "December, 2008." Title from electronic thesis title page (viewed 12/12/2009) Advisor, Dale H. Mugler; Committee members, Daniel B. Sheffer, Bruce C. Taylor; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / Department of Biology

Hypoglycemia is one of the most serious acute complications in intensively treated diabetes. Recurrent hypoglycemia predisposes individuals to subsequent hypoglycemia, and diminished counterregulatory hormone responses increase this threat. Elevated pancreatic and/or circulating somatostatin has been reported in diabetic humans and animals, and we postulated that excessive somatostatin contributes to the attenuation of counterregulatory hormone release during hypoglycemia in diabetes. It is known that somatostatin suppresses stimulated secretion of glucagon, epinephrine, and corticosterone. We hypothesized that selective somatostatin receptor type 2 (SSTR2) antagonism would: (Study 1) improve hormone counterregulation to hypoglycemia, and (Study 2) ameliorate hypoglycemia in recurrently hypoglycemic rats. Using both high (10 U/kg) and low (5 U/kg) dose insulin to induce hypoglycemia, we demonstrate that inhibiting the action of somatostatin on SSTR2 normalizes the severely attenuated glucagon and corticosterone responses to acute hypoglycemia in diabetic rats. These improvements were specific to diabetes since SSTR2 antagonism did not increase these hormones in non-diabetic rats in response to hypoglycemia. In the absence of hypoglycemia, SSTR2 antagonist neither markedly alters glycemia nor causes sustained elevations in counterregulatory hormones in diabetic animals. Diabetic rats exhibit up to 65% and 75% more pancreatic and plasma somatostatin than non-diabetic rats following hypoglycemia, respectively. Despite improvements of glucagon and corticosterone, expression of gluconeogenic enzymes PEPCK1 and G6Pase was unaltered. SSTR2 antagonism reduced the glucose requirement during a hypoglycemic clamp induced with a lower dose of insulin. In recurrently hypoglycemic diabetic rats, we demonstrate that SSTR2 antagonist treatment reduces the depth and duration of hypoglycemia and promotes the recovery to euglycemia, without affecting the glycemia-lowering effect of insulin. This amelioration of hypoglycemia by SSTR2 antagonism may be attributable in part to the observed modest improvements of glucagon, epinephrine, and corticosterone counterregulation following recurrent hypoglycemia. These results implicate an important role for increased pancreatic, and possibly circulating, somatostatin in defective hypoglycemic counterregulation in diabetes.

[Truncated abstract] Exercise is generally recommended for individuals with type 1 diabetes mellitus since it is associated with numerous physiological and psychological benefits. However, participation in exercise can also increase the risk of experiencing severe hypoglycaemia both during exercise and recovery. Unfortunately, existing guidelines to minimise the risk of exercise-induced hypoglycaemia are often general and fail to take into account that different precautions are required for exercise of varying type, duration and intensity. Specifically, there are no evidence-based guidelines for safe participation in intermittent high-intensity exercise (IHE), which characterises the activity patterns of most team and field sports, manual labour occupations and spontaneous play in children. This is because the response of blood glucose levels to this type of exercise is not known. Consequently, the purpose of this thesis was to investigate the glucoregulatory responses to IHE that replicates the high-intensity work-to-recovery ratios observed in intermittent sports in individuals with type 1 diabetes, in order to assess the associated risk of hypoglycaemia. The first study of this thesis examined the effect of the repeated bouts of high-intensity exercise that characterise IHE compared to remaining inactive, on blood glucose and glucoregulatory hormone levels in individuals with type 1 diabetes. Eight healthy individuals with type 1 diabetes were tested on two separate occasions during which either a 20 minute rest (CON) or an IHE protocol designed to simulate the activity patterns of team sports was performed (repeated 4 second sprints every 2 minutes). ... During the second hour of recovery, Ra and Rd returned to baseline following MOD, but remained elevated after IHE. These changes in Ra and Rd were consistent with a lower glucose infusion rate (GIR) during early recovery from IHE and a higher GIR after 2 hours of recovery compared to MOD. In conclusion, the repeated bouts of high-intensity exercise associated with IHE stimulate a more rapid and greater increment in Ra during exercise and attenuate glucose Rd during early recovery. These findings assist in explaining, in part, the previous observation that the risk of hypoglycaemia might be lower during IHE and early recovery compared to MOD. Overall, the findings of this thesis have implications for current recommendations aimed at managing blood glucose levels during and after exercise to avoid hypoglycaemia.

Licentiatavhandling (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 2 uppsatser.