Food image-induced brain activation is not diminished by insulin infusion.

BACKGROUND/OBJECTIVES: The obesity epidemic appears to be driven in large part by our modern environment inundated by food cues, which may influence our desire to eat. Although insulin decreases food intake in both animals and humans, the effect of insulin on motivation for food in the presence of food cues is not known. Therefore, the aim of this study was to evaluate the effect of an intravenous insulin infusion on the brain response to visual food cues, hunger and food craving in non-obese human subjects. SUBJECTS/METHODS: Thirty-four right-handed healthy non-obese subjects (19F/15M, age: 29±8 years.; BMI: 23.1±2.1 kg m-2) were divided in two groups matched by age and BMI; the insulin group (18 subjects) underwent a hyperinsulinemic-euglycemic-clamp, and the control group (16 subjects) received an intravenous saline infusion, while viewing high and low-calorie food and non-food pictures during a functional MRI scan. Motivation for food was determined via analog scales for hunger, wanting and liking ratings. RESULTS: Food images induced brain responses in the hypothalamus, striatum, amygdala, insula, ventromedial prefrontal cortex (PFC), dorsolateral PFC and occipital lobe (whole brain correction, P<0.05). Wanting (P<0.001) and liking (P<0.001) ratings were significantly higher for the food than the non-food images, but not different between insulin and saline infusion groups. Hunger ratings increased throughout the MRI scan and correlated with preference for high-calorie food pictures (r=0.70; P<0.001). However, neither brain activity nor food cravings were affected by hyperinsulinemia or hormonal status (leptin and ghrelin levels) (P=NS). CONCLUSIONS: Our data demonstrate that visual food cues induce a strong response in motivation/reward and cognitive-executive control brain regions in non-obese subjects, but that these responses are not diminished by hyperinsulinemia per se. These findings suggest that our modern food cue saturated environment may be sufficient to overpower homeostatic hormonal signals, and thus contribute to the current obesity epidemic.

Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. METHODS: To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. RESULTS: Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% (p < 0.05) with RYGB, whereas the effect of insulin on HGP was completely absent in VMH IR knockdown (IRkd) rats. By contrast, both RYGB groups displayed an identical twofold increase in insulin-stimulated peripheral glucose uptake. The animals that underwent control gastrointestinal surgery failed to show any improvement in either hepatic or peripheral insulin sensitivity; VMH IRkd did not influence the magnitude of insulin resistance. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that RYGB surgery in high-fat-fed obese rats enhances hepatic and peripheral insulin sensitivity independently of weight loss. The improved hepatic, but not the peripheral, response to insulin is mediated centrally at the level of the VMH. These data provide direct evidence that the metabolic benefits of RYGB surgery are not simply a consequence of weight loss but likely in part involve the central nervous system.

Severe sepsis in the emergency department: an observational cohort study from the university hospital of the West Indies / Sepsis severa en la sala de emergencias: un estudio observacional de cohorte en el hospital universitario de West Indies

OBJECTIVE: To describe the incidence, treatment and outcomes of patients with severe sepsis and septic shock in a setting where early goal directed therapy (EGDT) is not routinely performed. METHOD: An observational study of all adult patients admitted from the emergency department (ED) of the University Hospital of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment patterns and inhospital outcomes were evaluated. RESULTS: A total of 58 011 patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49% were female. Medical history included hypertension (29%), diabetes mellitus (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of sepsis were pneumonia (67%) and urinary tract infection (46%). Median, interquartile range (IQR) time from triage to antibiotic administration was 126 (88, 220) minutes and antibiotics were given to 65.7% within three hours. Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR) lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward; 1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length of hospital stay was 9.5 (10.3) days. Inhospital mortality was 25% and survival correlated inversely with age (r pb = 0.25; p = 0.006). CONCLUSION: Despite a lack of EGDT, sepsis treatment patterns were consistent with "bestpractice" and mortality was lower than international comparators.

OBJETIVO: Describir la incidencia, el tratamiento y los resultados para pacientes con sepsis severa y shock séptico en un entorno donde la terapia dirigida por metas tempranas (TDMT) no se realiza de modo rutinario. MÉTODO: Se realizó un estudio observacional de todos los pacientes adultos con diagnóstico de sepsis severa y shock séptico, ingresados en la Sala de Emergencias del Hospital Universitario de West Indies (HUWI) desde el 5 de julio de 2007 al 1ero. de septiembre de 2008. Se evaluaron los parámetros iniciales de referencia, los patrones de tratamiento, y la evolución intrahospitalaria. RESULTADOS: Un total de 58 011 pacientes fueron vistos, 762 (1.3%) de ellos con sepsis. De estos casos con sepsis, 117 (15.4%) fueron clasificados como sepsis severa o shock séptico. La edad media (SD) fue 59.2 (23.3) años y 49% eran mujeres. Historia clínica incluía hipertensión (29%), diabetes (26%), accidente cerebrovascular (8%), insuficiencia cardíaca (6%) y VIH (6%). Las fuentes más comunes de la sepsis fueron neumonía (67%) e infección del tracto urinario (46%). La mediana del tiempo (IQR) transcurrido desde la selección (triaje) hasta la administración de antibióticos fue 126 (88, 220) minutos, y los antibióticos fueron entregados al 65.7% dentro de las tres horas. En general, los organismos fueron sensibles a los antibióticos empíricos en 69%. La mediana del lactato (IQR) fue 5.3 (4.5, 7.5) mmol/L. La mayoría de los pacientes (95%) fueron ingresados a la sala; 1% se destinó a la unidad de cuidados intensivos (UCI), y el 2% murió en la Sala de Emergencias. El promedio (SD) de la estancia hospitalaria fue de 9.5 (10.3) días. La mortalidad intrahospitalaria fue de 25%, y la supervivencia se halló en correlación inversa con la edad (rpb = .25; p = 0.006). CONCLUSIÓN: A pesar de la falta de TDMT, los patrones del tratamiento de sepsis fueron consistentes con las "mejores prácticas", y la mortalidad fue menor comparada con los datos de comparación a nivel internacional.

Severe sepsis in the emergency department - an observational cohort study from the university hospital of the West Indies.

OBJECTIVE: To describe the incidence, treatment and outcomes of patients with severe sepsis and septic shock in a setting where early goal directed therapy (EGDT) is not routinely performed. METHOD: An observational study of all adult patients admitted from the emergency department (ED) of the University Hospital of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment patterns and in-hospital outcomes were evaluated. RESULTS: A total of 58 011 patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49% were female. Medical history included hypertension (29%), diabetes mellitus (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of sepsis were pneumonia (67%) and urinary tract infection (46%). Median, interquartile range (IQR) time from triage to antibiotic administration was 126 (88, 220) minutes and antibiotics were given to 65.7% within three hours. Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR) lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward; 1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length of hospital stay was 9.5 (10.3) days. In-hospital mortality was 25% and survival correlated inversely with age (rpb = -0.25; p = 0.006). CONCLUSION: Despite a lack of EGDT, sepsis treatment patterns were consistent with "best-practice" and mortality was lower than international comparators.

Year in diabetes 2012: The diabetes tsunami.

Diabetes affects more than 300 million individuals globally, contributing to significant morbidity and mortality worldwide. As the incidence and prevalence of diabetes continue to escalate with the force of an approaching tsunami, it is imperative that we better define the biological mechanisms causing both obesity and diabetes and identify optimal prevention and treatment strategies that will enable a healthier environment and calmer waters. New guidelines from the American Diabetes Association/European Association of the Study of Diabetes and The Endocrine Society encourage individualized care for each patient with diabetes, both in the outpatient and inpatient setting. Recent data suggest that restoration of normal glucose metabolism in people with prediabetes may delay progression to type 2 diabetes (T2DM). However, several large clinical trials have underscored the limitations of current treatment options once T2DM has developed, particularly in obese children with the disease. Prospects for reversing new-onset type 1 diabetes also appear limited, although recent clinical trials indicate that immunotherapy can delay the loss of ß-cell function, suggesting potential benefits if treatment is initiated earlier. Research demonstrating a role for the central nervous system in the development of obesity and T2DM, the identification of a new hormone that simulates some of the benefits of exercise, and the development of new ß-cell imaging techniques may provide novel therapeutic targets and biomarkers of early diabetes detection for optimization of interventions. Today's message is that a diabetes tsunami is imminent, and the only way to minimize the damage is to create an early warning system and improve interventions to protect those in its path.

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging.

AIMS/HYPOTHESIS: Loss of pancreatic beta cell mass and function leads to the development of diabetes mellitus. Currently there is no technical way to non-invasively image islet function and mass. Murine models suggest that islets are highly vascularised organs that make a significant contribution to the total pancreatic blood flow. The current study was undertaken to test with arterial spin labelling (ASL) magnetic resonance imaging if islet mass and/or stimulation of human pancreatic islets by hyperglycaemia can differentially increase whole-pancreas perfusion, thereby distinguishing non-diabetic from type 1 diabetic patients. METHODS: We assessed pancreatic blood flow using ASL at baseline, during a hyperglycaemia clamp study (glucose at 11 mmol/l) and during recovery to euglycaemia. RESULTS: Seventeen healthy volunteers and seven type 1 diabetic patients were studied. In healthy volunteers we observed no change in pancreatic blood flow during the three phases of the study. A trend for an increase in blood flow was observed in the two control tissues, the liver and kidney. Similarly, there was no significant difference in blood flow during the three stages (baseline, hyperglycaemia and recovery) in diabetic patients and there was no significant difference observed between diabetic patients and normal volunteers. CONCLUSIONS/INTERPRETATION: Our data suggest that in humans neither increased demand nor islet mass has a substantial influence on pancreatic perfusion. It is possible, however, that the current state-of-the art imaging technology employed in this study might not be sensitive enough to distinguish between a true effect and noise. TRIAL REGISTRATION: ClinicalTrials.gov NCT00280085.

The association of birth weight with arterial stiffness at mid-adulthood: the Bogalusa Heart Study.

BACKGROUND: Birth weight has been found to predict cardiovascular morbidity and mortality. Pulse wave velocity (PWV), a marker of arterial stiffness, has been associated with cardiovascular risk factors. An association between birth weight and blood pressure (BP) has previously been reported. In this study, the association of birth weight with PWV, and the relationship between birth weight, pulse wave velocity and BP in mid-adulthood were investigated. METHODS: The Bogalusa Heart Study (BHS) is a population-based longitudinal study to investigate the natural development of cardiovascular risk factors. In the 2001 survey, brachial-ankle PWV (baPWV) was measured as an indicator of arterial stiffness. Of the 1203 participants in that survey, 707 had complete data on birth weight and PWV, which were utilised for this study. RESULTS: In this study, birth weight was inversely correlated with baPWV, pulse pressure, and systolic and diastolic BP (r = -0.10; r = -0.10; r = -0.13 and r = -0.09, respectively; p< or =0.01 for all). After adjustment, birth weight was inversely associated with baPWV. On average, baPWV decreased by 0.23 m/s (95% CI -0.44 to -0.03 m/s) for each 1 kg increase in birth weight. Birth weight (inversely) and baPWV were independently associated with systolic BP (B = -2.05; 95% CI -3.27 to -0.84 and B = 2.99; 95% CI 2.58 to 3.40 respectively). CONCLUSIONS: Lower birth weight is associated with higher baPWV. The link between birth weight and systolic BP may be partially explained by the association of birth weight with PWV.

Hypothalamic AMP-activated protein kinase activation with AICAR amplifies counterregulatory responses to hypoglycemia in a rodent model of type 1 diabetes.

In nondiabetic rodents, AMP-activated protein kinase (AMPK) plays a role in the glucose-sensing mechanism used by the ventromedial hypothalamus (VMH), a key brain region involved in the detection of hypoglycemia. However, AMPK is regulated by both hyper- and hypoglycemia, so whether AMPK plays a similar role in type 1 diabetes (T1DM) is unknown. To address this issue, we used four groups of chronically catheterized male diabetic BB rats, a rodent model of autoimmune T1DM with established insulin-requiring diabetes (40 +/- 4 pmol/l basal c-peptide). Two groups were subjected to 3 days of recurrent hypoglycemia (RH), while the other two groups were kept hyperglycemic [chronic hyperglycemia (CH)]. All groups subsequently underwent hyperinsulinemic hypoglycemic clamp studies on day 4 in conjunction with VMH microinjection with either saline (control) or AICAR (5-aminoimidazole-4-carboxamide) to activate AMPK. Compared with controls, local VMH application of AICAR during hypoglycemia amplified both glucagon [means +/- SE, area under the curve over time (AUC/t) 144 +/- 43 vs. 50 +/- 11 ng.l(-1).min(-1); P < 0.05] and epinephrine [4.27 +/- 0.96 vs. 1.06 +/- 0.26 nmol.l(-1).min(-1); P < 0.05] responses in RH-BB rats, and amplified the glucagon [151 +/- 22 vs. 85 +/- 22 ng.l(-1).min(-1); P < 0.05] response in CH-BB rats. We conclude that VMH AMPK also plays a role in glucose-sensing during hypoglycemia in a rodent model of T1DM. Moreover, our data suggest that it may be possible to partially restore the hypoglycemia-specific glucagon secretory defect characteristic of T1DM through manipulation of VMH AMPK.

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

The association of birth weight with developmental trends in blood pressure from childhood through mid-adulthood: the Bogalusa Heart study.

Low birth weight has been found to be associated with cardiovascular mortality and morbidity and with an adverse profile of several cardiovascular risk factors. The inverse association between birth weight and blood pressure was consistently reported from many populations. Using longitudinal data from the Bogalusa Heart Study (Louisiana), the authors investigated the association between birth weight and progression of blood pressure through early adulthood, comparing that relation between African Americans and Whites. Birth data of 2,275 participants, screened two or more times in the Bogalusa Heart Study between 1973 and 2001, were retrospectively obtained from birth certificates and were linked to their clinical, laboratory, and socioeconomic and lifestyle data in the Bogalusa Heart Study data sets. Birth weight was inversely associated with systolic blood pressure, diastolic blood pressure, and pulse pressure (p

Influence of acute alcohol ingestion on the hormonal responses to modest hypoglycaemia in patients with Type 1 diabetes.

AIMS: To determine whether mild alcohol intoxication (45-50 mg/dl) influences counterregulatory hormone responses to moderate hypoglycaemia (2.8 mmol/l)in patients with Type 1 diabetes. METHODS: Seventeen subjects (14 male, age range 21-46 years) with Type 1 diabetes underwent four hyperinsulinaemic glucose clamps: euglycaemia with placebo; euglycaemia with alcohol (0.4 g/kg); hypoglycaemia (2.8 mmol/l for 65 min)with placebo; and hypoglycaemia (2.8 mmol/l for 65 min) with alcohol (0.4 g/kg). Arterialized venous blood samples were taken for measurement of insulin and counterregulatory hormones. RESULTS: During hypoglycaemia, peak growth hormone concentrations were significantly lower after alcohol compared with placebo (14.3 +/- 2.9 vs.25.9 +/- 3.4 microg/l,P< 0.001) associated with reduced insulin sensitivity in both hypoglycaemia and euglycaemia studies. CONCLUSIONS: We found an attenuated growth hormone response to hypoglycaemia associated with mild alcohol intoxication. Although this may potentially contribute to impaired recovery of glucose after hypoglycaemia in patients with Type 1 diabetes, it appears to be offset by a reduction in insulin action.

[Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. (A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes)].

This Russian translation and reprint of the original article published with authors permissions. Original article published in the Diabetes Care. 2006;29(8). Translation to Russian prepared by Yu. Sych. An abridged version of the article was prepared by A. Gorbovskaya. These recommendations and the algorithm are based on data from clinical studies of various treatment options for type 2 diabetes and on the personal experience of consensus participants, taking into account the main goal of treatment - to achieve and maintain glucose levels as close as possible to glycemia in healthy people. The lack of evidence of high levels of glycemia obtained in comparative clinical trials with a direct comparison of different treatment options for diabetes remains the main obstacle to isolating one main class of drugs or combination of drugs that have advantages over others.

Prevalence and genetic diversity of Entamoeba histolytica in an institution for the mentally retarded in the Philippines.

A total of 113 mentally retarded patients residing in a mental institution in Metropolitan Manila, Philippines, were screened for the presence of Entamoeba histolytica based on microscopy and polymerase chain reaction (PCR). Anti-E. histolytica antibodies were also screened in 97 serum samples collected using immunofluorescence antibody (IFA) test. Parasitological examination showed E. histolytica/Entamoeba dispar in 43 cases (38.05%), while PCR detected 74 cases (65.48%) positive for E. histolytica and 6 cases (5.30%) positive for E. dispar. Interestingly, these 6 samples were coinfected with E. histolytica. IFA test revealed that 80.41% (78/97) of the respondents possessed significant antibody titers for intestinal infection of E. histolytica. Of this number, there were 5 patients negative in IFA test but positive in PCR. The genetic diversity of E. histolytica isolates was also investigated by analyzing polymorphism in the serine-rich gene by nested PCR on DNA directly extracted from stool specimens. A combination of the nested PCR results and the AluI digestion of the PCR products examined yielded six distinct DNA banding patterns among the 74 stool isolates. An apparent clustering of E. histolytica strains was observed in patients living in different residential cottages of the institution. These results indicate the high prevalence of E. histolytica in an institution for the mentally retarded in the Philippines.

Targeted expression of the anti-apoptotic gene CrmA to NOD pancreatic islets protects from autoimmune diabetes.

The activation of apoptosis is a critical mechanism by which pancreatic beta cells are destroyed in type 1 diabetes (T1DM). Strategies aimed at interfering with the apoptotic pathways could therefore be of potential therapeutic value. To this end, we generated NOD transgenic mice with targeted expression of the anti-apoptotic gene Cytokine response modifier A (CrmA) to pancreatic beta cells using the rat insulin promoter and the reverse tetracycline transactivator to express CrmA in a temporally controlled manner. Two lines of transgenic mice were studied whose expression of CrmA occurred only after feeding doxycycline food. Islet expression of CrmA partially protected pancreatic beta cells from the cytokine-mediated cytotoxicity in vitro and reduced modestly the spontaneous development of diabetes in NOD mice in vivo. In addition, beta cells from NOD CrmA mice were significantly protected from the destruction by diabetogenic T cells after adoptive transfer. More strikingly, NODCrmA mice were significantly resistant to the diabetogenic activity of a potent insulin-specific CD8 T-cell clone. Since these adoptive transfer models mainly represent the effector phase rather than the initiation phase of autoimmune diabetes, our data suggest that the latter is more sensitive to CrmA protection. We conclude that anti-apoptotic genes such as CrmA might be potential candidates to enhance islet graft survival in T1DM.

Origins of the "black/white" difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study.

BACKGROUND: The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence. METHODS AND RESULTS: Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years. CONCLUSIONS: If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.

Influence of alcohol on cognitive performance during mild hypoglycaemia; implications for Type 1 diabetes.

AIMS: Alcohol and hypoglycaemia independently affect cognitive function. This may be relevant for insulin-treated diabetic patients who drive motor vehicles. The aim of this study was to examine the effect of mild hypoglycaemia (2.8 mmol/l) with modest alcohol intoxication (levels below UK driving limits) on intellectual performance in patients with Type 1 diabetes. METHODS: A hyperinsulinaemic glucose clamp (60 mU/m2) was used to study 17 subjects [age 35 +/- 8 years, HbA1c 8.1 +/- 1.4% (mean +/- sd)] on four occasions: (A) euglycaemia (4.5 mmol/l) with placebo, (B) euglycaemia with alcohol, (C) hypoglycaemia (2.8 mmol/l) with placebo, and (D) hypoglycaemia with alcohol. Cognitive performance was assessed using four-choice reaction time (4CRT, primary outcome), measurements of general intellectual skills [trail making B (TMB) and digit symbol substitution (DSST)], and visual information processing [visual change detection (VCD)]. A test related to driving performance (hazard perception) was also used. RESULTS: In experiments B and D the average blood alcohol level was 43 mg/dl. This was associated with deterioration in 4CRT [+ 35 ms [95% confidence interval (CI) 20, 50]] and TMB, whereas hypoglycaemia without alcohol increased 4CRT only [+ 39 ms (95% CI 5, 73)]. However, when alcohol was combined with hypoglycaemia, there was marked deterioration in all the cognitive function tests [4CRT 74 ms (95% CI 35, 113), TMB, DSST and VCD]. Hazard perception was not affected. The effect of alcohol was no different in euglycaemia than in hypoglycaemia, i.e. there was no interaction. Whereas hypoglycaemia did not reduce the likelihood that the subjects would drive, alcohol did. CONCLUSIONS: The cumulative effect of alcohol and hypoglycaemia on cognitive function together has implications for driving in patients with Type 1 diabetes. Both independently impair cognitive function and together the effects are additive. Patients with Type 1 diabetes should be educated about hypoglycaemia and driving and should avoid alcohol completely if planning to drive.

Effects of recurrent antecedent hypoglycaemia and chronic hyperglycaemia on brainstem extra-cellular glucose concentrations during acute hypoglycaemia in conscious diabetic BB rats.

AIMS/HYPOTHESIS: Our aim was to determine whether the divergent effects of chronic exposure to hyperglycaemia or hypoglycaemia on the glycaemic threshold for auditory brainstem dysfunction are reflected in the extra-cellular fluid (ECF) concentrations of glucose in the inferior colliculus during hypoglycaemia in the diabetic BB rat. METHODS: Microdialysis was used to measure inferior colliculus ECF glucose concentrations under basal and hyperinsulinaemic (20 mU/kg.min) hypoglycaemic conditions. RESULTS: ECF glucose is increased under basal (hyperglycaemic) conditions and decreases during hypoglycaemia in both recurrently hypoglycaemic and chronically hyperglycaemic diabetic BB rats (to 0.5+/-0.1 and 0.8+/-0.2 mmol/L respectively), with no significant differences between groups. In both groups the plasma to ECF glucose ratio doubled during hypoglycaemia. CONCLUSION/INTERPRETATION: Prior exposure to recurrent hypoglycaemia does not lead to increased ECF glucose concentrations in the inferior colliculus of diabetic BB rats. The resistance to impaired brainstem function seen in recurrently hypoglycaemic rats during hypoglycaemia cannot simply be attributed to increased blood-brain barrier glucose transport within this brain region.