Hypoglycemic coma masquerading thyrotoxic storm.
(49/2319)
A 59-year-old woman was hospitalized in hypoglycemic coma. Although hypoglycemia was promptly reversed, she was in a somnolent, restless state with tachycardia, tremor, profuse sweating, and high body temperature. Thyrotoxic storm was highly suspected and vigorous antithyroid regimens gradually brought her up to normal mental and cardiovascular states in several days. However, profound generalized myopathy necessitated the maintenance with a respirator. One month later, an episode of angina pectoris was followed by generalized convulsion, coma, and death in a few days. Neuroimaging study disclosed posterior leukoencephalopathy syndrome. This case is instructive in that hypoglycemic coma may masquerade the major symptomatology of thyrotoxic storm, and that profound myopathy and angiopathic or angiospastic processes of the brain and the heart may interfere with the outcome. (+info)
The role of nitric oxide in mediating pancreatic endocrine responses to insulin-induced hypoglycaemia in the conscious calf.
(50/2319)
The role of nitric oxide (NO) in mediating pancreatic endocrine responses to moderate hypoglycaemia has been investigated in conscious unrestrained calves. The synthesis of endogenous NO was inhibited by the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mg kg-1 I.A.), while sodium nitroprusside was infused continuously (2-4 microg min-1 kg-1 I.V.) to mimic the tonic production of NO. This effectively abolished the rise in plasma pancreatic polypeptide (PP) concentration during moderate hypoglycaemia (0.7 nmol kg-1 insulin I.V.) and significantly reduced the response to more intense hypoglycaemia (2.0 nmol kg-1 insulin I. V.). In contrast, the glucagon response was not significantly affected in either group, although consistently higher plasma glucagon values were obtained in response to the higher dose of insulin following the administration of L-NAME. It is concluded that, in the absence of L-NAME, production of NO contributes to the PP response, but not the glucagon response to hypoglycaemia in this species under physiological conditions. (+info)
Brittle diabetes characterised by recurrent hypoglycaemia.
(51/2319)
There is little information on the clinical characteristics of "brittle" Type 1 (insulin-dependent) diabetic patients with predominantly hypoglycaemic instability. From a total cohort of 381 brittle diabetic patients from various parts of the United Kingdom, 64 (17%) had life-disrupting instability due to recurrent hospital admissions with hypoglycaemia. Compared to brittle patients with recurrent ketoacidosis (DKA), who comprised 59% of the total, those with recurrent hypoglycaemia were characterised by older mean age (34 +/- 20 v 22 +/- 11 y, p < 0.001), and more equal sex distribution (53% v 71% female, p < 0.05). Patients with "mixed brittleness" (24% of total) were intermediate between the other groups, in terms of both age and female predominance. Physicians in charge of patients with hypoglycaemic brittle diabetes considered psychosocial factors to be frequent underlying causes, though organic conditions such as lost hypoglycaemic warnings and alcohol abuse were also mentioned. Factitious insulin overdose was diagnosed in 3 patients. We conclude that hypoglycaemic brittle diabetes is a small but important sub-group of the overall brittle syndrome. It differs in age and sex distribution from the more common syndrome of recurrent DKA. (+info)
Engineering a glucose-responsive human insulin-secreting cell line from islets of Langerhans isolated from a patient with persistent hyperinsulinemic hypoglycemia of infancy.
(52/2319)
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia. We have discovered that islet cells, isolated from the pancreas of a PHHI patient, proliferate in culture while maintaining a beta cell-like phenotype. The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose. In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression. To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1. One selected clonal cell line (NISK9) had normal K(ATP) channel activity, and as a result of changes in intracellular Ca(2+) homeostasis ([Ca(2+)](i)) secreted insulin within the physiological range of glucose concentrations. This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus. (+info)
Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease.
(53/2319)
Hyperphosphorylated tau is the major component of paired helical filaments in neurofibrillary tangles found in Alzheimer's disease brains, and tau hyperphosphorylation is thought to be a critical event in the pathogenesis of this disease. The objective of this study was to reproduce tau hyperphosphorylation in an animal model by inducing hypoglycemia. Food deprivation of mice for 1 to 3 days progressively enhanced tau hyperphosphorylation in the hippocampus, to a lesser extent in the cerebral cortex, but the effect was least in the cerebellum, in correspondence with the regional selectivity of tauopathy in Alzheimer's disease. This hyperphosphorylation was reversible by refeeding for 1 day. We discuss possible mechanisms of this phenomenon, and propose the starved mouse as a simple model to study in vivo tau phosphorylation and dephosphorylation which are altered in Alzheimer's disease. (+info)
Educational guidelines for achieving tight control and minimizing complications of type 1 diabetes.
(54/2319)
Tight glucose control with intensive therapy in patients with type 1 diabetes (formerly known as juvenile-onset or insulin-dependent diabetes) can delay the onset and slow the progression of retinopathy, nephropathy and neuropathy. Optimal blood glucose control is defined by a target glycosylated hemoglobin level of less than 7 percent, a preprandial glucose level of 80 to 120 mg per dL (4.4 to 6.7 mmol per L) and a bedtime glucose level of 100 to 140 mg per dL (5.6 to 7.8 mmol per L). This article provides guidelines to help family physicians teach patients with type 1 diabetes how to achieve tight glucose control to help minimize complications. Guidelines include maintaining blood glucose levels at near normal by taking doses of short-acting insulin throughout the day supplemented by a nighttime dose of intermediate-acting insulin, monitoring blood glucose levels frequently, following a prudent diet, exercising regularly and effectively managing hypoglycemia, as well as empowering patients to lead their control efforts and rigorously controlling other risk factors for cardiovascular disease. Support from physicians, family members and friends is crucial to the success of a regimen of tight glucose control. (+info)
Biopsychobehavioral model of severe hypoglycemia. II. Understanding the risk of severe hypoglycemia.
(55/2319)
OBJECTIVE: To evaluate the clinical/research utility of the biopsycho-behavioral model of severe hypoglycemia in differentiating patients with and without a history of severe hypoglycemia and in predicting occurrence of future severe hypoglycemia. RESEARCH DESIGN AND METHODS: A total of 93 adults with type 1 diabetes (mean age 35.8 years, duration of diabetes 16 +/- 10 years, HbA1 8.6 +/- 1.8%), 42 of whom had a recent history of recurrent severe hypoglycemia (SH) and 51 who did not (NoSH), used a handheld computer for 70 trials during 1 month recording cognitive-motor functioning, symptoms, blood glucose (BG) estimates, judgments concerning self-treatment of BG, actual BG readings, and actual treatment of low BG. For the next 6 months, patients recorded occurrence of severe hypoglycemia. RESULTS: SH patients demonstrated significantly more frequent and extreme low BG readings (low BG index), greater cognitive-motor impairments during hypoglycemia, fewer perceived symptoms of hypoglycemia, and poorer detection of hypoglycemia. SH patients were also less likely to treat their hypoglycemia with glucose and more likely to treat with general foods. Low BG index, magnitude of hypoglycemia-impaired ability to do mental subtraction, and awareness of neuroglycopenia, neurogenic symptoms, and hypoglycemia correlated separately with number of SH episodes in the subsequent 6 months. However, only low BG index, hypoglycemia-impaired ability to do mental subtraction, and awareness of hypoglycemia entered into a regression model predicting future severe hypoglycemia (R2 = 0.25, P < 0.001). CONCLUSIONS: Patients with a history of severe hypoglycemia differed on five of the seven steps of the biopsychobehavioral model of severe hypoglycemia. Helping patients with a recent history of severe hypoglycemia to reduce the frequency of their low-BG events, become more sensitive to early signs of neuroglycopenia and neurogenic symptoms, better recognize occurrence of low BG, and use fast-acting glucose more frequently in the treatment of low BG, may reduce occurrence of future severe hypoglycemia. (+info)
Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia.
(56/2319)
OBJECTIVE: To analyze a transcutaneous near-infrared spectroscopy system as a technique for in vivo noninvasive blood glucose monitoring during euglycemia and hypoglycemia. RESEARCH DESIGN AND METHODS: Ten nondiabetic subjects and two patients with type 1 diabetes were examined in a total of 27 studies. In each study, the subject's plasma glucose was lowered to a hypoglycemia level (approximately 55 mg/dl) followed by recovery to a glycemic level of approximately 115 mg/dl using an intravenous infusion of insulin and 20% dextrose. Plasma glucose levels were determined at 5-min intervals by standard glucose oxidase method and simultaneously by a near-infrared spectroscopic system. The plasma glucose measured by the standard method was used to create a calibration model that could predict glucose levels from the near-infrared spectral data. The two data sets were correlated during the decline and recovery in plasma glucose, within 10 mg/dl plasma glucose ranges, and were examined using the Clarke Error Grid Analysis. RESULTS: Two sets of 1,704 plasma glucose determinations were examined. The near-infrared predictions during the fall and recovery in plasma glucose were highly correlated (r = 0.96 and 0.95, respectively). When analyzed during 10 mg/dl plasma glucose segments, the mean absolute difference between the near-infrared spectroscopy method and the chemometric reference ranged from 3.3 to 4.4 mg/dl in the nondiabetic subjects and from 2.6 to 3.8 mg/dl in the patients with type 1 diabetes. Using the Error Grid Analysis, 97.7% of all the near-infrared predictions were assigned to the A-zone. CONCLUSIONS: Our findings suggest that the near-infrared spectroscopy method can accurately predict plasma glucose levels during euglycemia and hypoglycemia in humans. (+info)