Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects.

BACKGROUND: Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). METHODS: Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. RESULTS: Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. CONCLUSION: The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.

Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics.

BACKGROUND: Triglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL). METHODS: Mass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting. RESULTS: The kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2 . It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2 . ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day-1 , and the increment during absorption was about 230 mg day-1 . The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. DISCUSSION: This novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: a twin study.

BACKGROUND: Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors. METHODS: We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins. RESULTS: ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance. CONCLUSIONS: The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors.

Anaesthetic-induced cardioprotection in an experimental model of the Takotsubo syndrome - isoflurane vs. propofol.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic doses of isoflurane, propofol and ketamine+midazolam on haemodynamics, global and regional LV systolic function and the activation of intracellular metabolic pathways in experimental TS. We hypothesized that cardioprotection in experimental TS is specific for isoflurane. METHODS: Forty-five rats were randomized to isoflurane (0.6 MAC, n = 15), propofol (bolus 200 mg/kg+360 mg/kg/h, n = 15) or ketamine (100 mg/kg)+midazolam (10 mg/kg, n = 15) anaesthesia. Arterial pressure, heart rate and body temperature were continuously measured and arterial blood gas analysis was performed intermittently. TS was induced by intraperitoneal injection of isoprenaline, 50 mg/kg. LV echocardiography was performed 90 min after isoprenaline injection. Apical cardiac tissue was analysed by global discovery proteomics and pathway analysis. RESULTS: Isoprenaline-induced changes in arterial blood pressure, heart rate or body temperature did not differ between groups. LV ejection fraction was higher and extent of LV akinesia was lower with isoflurane, when compared with the propofol and the ketamine+midazolam groups. In this TS-model, the proteomic analysis revealed an up-regulation of pathways involved in inflammation, coagulation, endocytosis and lipid metabolism. This up-regulation was clearly attenuated with isoflurane compared to propofol. CONCLUSION: In an experimental model of TS, isoflurane, but not propofol, exerts a cardioprotective effect. The proteomic analysis suggests that inflammation might be involved in pathogenesis of TS.

A genetic determinant of the striatal dopamine response to alcohol in men.

Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.

Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders.

Prior work suggests a role of kappa-opioid signaling in the control of alcohol drinking, in particular when drinking is escalated due to alcohol-induced long-term neuroadaptations. Here, we examined the small molecule selective kappa antagonist CERC-501 in rat models of alcohol-related behaviors, with the objective to evaluate its potential as a candidate therapeutic for alcohol use disorders. We first tested the effect of CERC-501 on acute alcohol withdrawal-induced anxiety-like behavior. CERC-501 was then tested on basal as well as escalated alcohol self-administration induced by 20% alcohol intermittent access. Finally, we determined the effects of CERC-501 on relapse to alcohol seeking triggered by both stress and alcohol-associated cues. Control experiments were performed to confirm the specificity of CERC-501 effects on alcohol-related behaviors. CERC-501 reversed anxiety-like behavior induced by alcohol withdrawal. It did not affect basal alcohol self-administration but did dose-dependently suppress self-administration that had escalated following long-term intermittent access to alcohol. CERC-501 blocked relapse to alcohol seeking induced by stress, but not when relapse-like behavior was triggered by alcohol-associated cues. The effects of CERC-501 were observed in the absence of sedative side effects and were not due to effects on alcohol metabolism. Thus, in a broad battery of preclinical alcohol models, CERC-501 has an activity profile characteristic of anti-stress compounds. Combined with its demonstrated preclinical and clinical safety profile, these data support clinical development of CERC-501 for alcohol use disorders, in particular for patients with negatively reinforced, stress-driven alcohol seeking and use.

The ansa cervicalis revisited.

Recurrent laryngeal nerve paralysis represents a major complication in oesophageal cancer surgery. Nerve-muscle transplantation to the paraglottic space after resection of the recurrent laryngeal nerve with the ansa cervicalis (AC) has recently become the procedure of choice. The aim of this study was to investigate the anatomical variations of AC in order to avoid iatrogenic injuries and facilitate surgical procedures. We examined 100 adult human formalin-fixed cadavers. The ansa cervicalis showed a great degree of variation regarding origin and distribution. The origin of the superior root of AC was found to be superior to the digastric muscle in 92% of the cases. Its vertical descent was found to be superficial to the external carotid artery in 72% and superficial to the internal carotid artery in 28% of the specimens. The inferior root of AC was derived from the primary rami of C2 and C3 in 38%, from C2, C3 and C4 in 10%, from C3 in 40% and from C2 in 12% of the cases. The inferior root passed posterolaterally to the internal jugular vein in 74% and anteromedially in 26% of the cases. The roots of AC were long (70%) or short (30%), and the union between the two roots was situated inferior or superior to the omohyoid. Not only is knowledge of the anatomy of the ansa cervicalis important for nerve grafting procedures, but surgeons should be aware of AC and its relationships to the great vessels of the neck in order to avoid inadvertent injury during surgical procedures of the neck.

Structural insights into the mode of action of a pure antiestrogen.

BACKGROUND: Estrogens exert their effects on target tissues by binding to a nuclear transcription factor termed the estrogen receptor (ER). Previous structural studies have demonstrated that each class of ER ligand (agonist, partial agonist, and SERM antagonist) induces distinctive orientations in the receptor's carboxy-terminal transactivation helix. The conformation of this portion of the receptor determines whether ER can recruit and interact with the components of the transcriptional machinery, thereby facilitating target gene expression. RESULTS: We have determined the structure of rat ERbeta ligand binding domain (LBD) in complex with the pure antiestrogen ICI 164,384 at 2.3 A resolution. The binding of this compound to the receptor completely abolishes the association between the transactivation helix (H12) and the rest of the LBD. The structure reveals that the terminal portion of ICI's bulky side chain substituent protrudes from the hormone binding pocket, binds along the coactivator recruitment site, and physically prevents H12 from adopting either its characteristic agonist or AF2 antagonist orientation. CONCLUSIONS: The binding mode adopted by the pure antiestrogen is similar to that seen for other ER antagonists. However, the size and resultant positioning of the ligand's side chain substituent produces a receptor conformation that is distinct from that adopted in the presence of other classes of ER ligands. The novel observation that binding of ICI results in the complete destabilization of H12 provides some indications as to a possible mechanism for pure receptor antagonism.

Anxiogenic-like action of galanin after intra-amygdala administration in the rat.

The neuropeptide galanin is expressed in brain structures implicated in regulation of emotionality. The amygdala is known to play a central role in mechanisms of fear and anxiety. We therefore examined the effects of galanin (0.2 and 0.6 nmol/side) on experimental anxiety upon microinjection into the amygdala. Two established animal models of anxiety were used: a punished drinking test, and the elevated plus-maze. Punished responding was dose dependently suppressed by intra-amygdala galanin, whereas unpunished responding, drinking motivation, locomotor activity, and shock thresholds were unaffected. No effects on experimental anxiety were seen in the plus-maze following galanin injection. When injected into parietal cortex, no anxiety promoting properties of galanin were detected. These data suggest that activation of galanin receptors in amygdala modulates neurotransmission involved in fear and experimental anxiety.

Local 5,7-dihydroxytryptamine lesions of rat amygdala: release of punished drinking, unaffected plus-maze behavior and ethanol consumption.

Several serotonergic drugs are effective for anxiety disorders, but underlying mechanisms are unclear, and findings in experimental animals are difficult to reconcile with human data. It has been proposed that differential effects of serotonin within specific anatomical systems may account for these difficulties, and the amygdala has been suggested as one of the structures involved. To examine this hypothesis, the neurotoxin 5,7-dihydroxytryptamine was administered locally in rat amygdala. Within the amygdala, serotonin was depleted by approximately 80%, with other transmitters unaffected, and serotonin transporter labelling was decreased by approximately 85%. Cortical areas near the lesion site were also affected, although to a lesser degree. Other forebrain areas were unaffected. Lesions resulted in a specific anti-conflict effect in a punished drinking test, but did not influence elevated plus-maze behavior (under baseline conditions and after restraint stress), locomotor activity or ethanol intake. These data suggest that the punished drinking test and the elevated plus-maze may activate different components of fear circuitry, and that the serotonergic input to the amygdala specifically participates in fear-related behavioral suppression mediated by this structure.

Lipid mediated gene delivery in the adult rat brain: quantitative analysis of expression.

Gene transfer into the adult brain is potentially an attractive alternative to commonly employed transgenic approaches. DNA-lipid complexes have been used to obtain brain gene transfer, but data are sparse to indicate to what extent this results in significant expression of functional protein. Here, an expression construct encoding the functional reporter, chloramphenicol-acetyl-transferase (CAT), was complexed to a novel biodegradable lipid, and delivered into the rat brain. CAT-activity was assayed in tissue extracts to allow a precise quantitation of functional enzyme protein. Following bilateral intraventricular (i.c.v.) injection, robust enzyme activity was found in all brain regions studied, peaking at 4 weeks. Other routes of administration, e.g. intra-parenchymal injection or chronic infusion of complexes, resulted in marginal or no activity. Presence of CAT mRNA and plasmid DNA in tissue extracts was confirmed at 4 weeks post i.c.v. administration. In agreement with previous studies, labelled lipid-DNA complexes were mainly found in the ventricular ependyma. Present data support the feasibility of lipid mediated brain gene transfer, and outline some of its anatomical and temporal limitations.

Behavioral and endocrine adaptation, and up-regulation of NPY expression in rat amygdala following repeated restraint stress.

A single 1 h restraint increases experimental anxiety in the elevated plus-maze through actions within the amygdala, while intra-amygdala administration of neuropeptide Y (NPY) has the opposite effect. Endogenous amygdala NPY expression is suppressed by single restraint, providing a possible mechanism for the anxiety-promoting action of this stressor. Here, we examined whether repeated stressor exposure might lead to an adaptation (habituation or sensitization) with regard to plus-maze behavior and glucocorticoid response, and whether this might be accompanied by altered effects of the stressor on NPY expression. Following repeated restraint (1 h/day, 9-10 days), neither an anxiogenic-like effect of the stressor nor a glucocorticoid response were present. This behavioral and endocrine adaptation was accompanied by an up-regulation of prepro-NPY mRNA and NPY peptide in amygdala but not in hypothalamic or cortical extracts, an effect opposite to that previously seen after a single restraint session. Thus, an up-regulation of NPY expression in the amygdala complex may be an adaptive mechanism recruited to cope with a repeated stressor.

Cationic lipid-mediated delivery and expression of prepro-neuropeptide Y cDNA after intraventricular administration in rat: feasibility and limitations.

The utility of in vivo lipofection for delivery and expression of a neuropeptide gene in the adult rat brain was explored. Prepro-neuropeptide Y (NPY) cDNA was cloned into the episomal eucaryotic expression vector pCEP4. This construct was complexed to lipofectamine or lipofectin. Complexed DNA was injected into the lateral ventricles of adult rats. Brains were removed for analysis following various time intervals. Polymerase chain reaction (PCR) reactions were designed for specific detection of endogenous and vector derived NPY sequence, respectively. PCR of DNA preparations from 5 major brain regions (frontal and parietal cortex, striatum, hypothalamus, brain stem) demonstrated presence of vector DNA up to 1 month (longest interval studied) in all brain regions. Reverse-transcription (RT-) PCR of DNase treated RNA-preparations from brain tissue demonstrated presence of both vector-derived and endogenous NPY mRNA in treated animals, while only endogenous mRNA was detected in controls. In situ hybridization histochemistry indicated scattered patches of vector uptake into tissue in the vicinity of the CSF compartment, but not into deeper located structures. Weight gain was not affected, indicating that the expression levels achieved may not be sufficient to play a functional role, and/or may need to be targeted to specific brain areas. These findings suggest a potential for cationic lipid mediated gene transfer in the brain as an experimental tool and as a possible future therapeutic principle, but also indicate the need for optimization of delivery strategies in order to achieve functionally relevant expression levels.

Suppressed neuropeptide Y (NPY) mRNA in rat amygdala following restraint stress.

We have previously demonstrated that NPY produces anxiolytic-like effects through actions in the amygdala, and that anxiogenic-like effects of restraint stress are mediated through this structure. Here, we examined the effects of restraint stress on NPY mRNA levels in amygdala and several other brain regions. A sensitive solution hybridization-RNase protection assay (RPA) was developed, employing a combination of internal and external standards, which allowed absolute quantitation of NPY mRNA in tissue-samples of less than 10 mg. NPY mRNA levels were determined, following a 1-h restraint stress, in homogenates of tissue from the amygdala, neocortex, striatum and hypothalamus, and the time course of these effects was examined. A highly significant decrease in NPY-mRNA levels was seen in the amygdala at 1 h and 2 h following restraint, with levels returning to normal within 10 h. A similar effect was seen in the neocortex, but was less pronounced and slower in onset. Striatal and hypothalamic NPY expression was not significantly affected. Tissue levels of NPY-peptide were modestly decreased in the amygdala at 1 h following restraint and had returned to normal within 4 h. The present findings support the hypothesis that anxiety related behavioral effects of stress may in part be mediated through modulation of NPY function in the amygdala.

Diverse functions of neuropeptide Y revealed using genetically modified animals.

Neuropeptide Y (NPY), a peptide abundantly expressed in the mammalian nervous system, has been extensively studied using traditional pharmacological and behavioral models. Central administration of NPY or synthetic ligands for its receptors has indicated a role of NPY in anxiety-related behaviors, feeding, regulation of blood pressure, circadian rhythm and other functions. Some limitations inherent in pharmacological approaches, such as lack of selectivity of receptor antagonists, can be elegantly circumvented using genetically modified animals. For NPY, mice lacking NPY, the Y1, the Y2 or the Y5 receptors have been generated. In addition, both mice and rats overexpressing NPY in the central nervous system are available. Here, we review the research carried out so far in the NPY-field using genetically modified animals. Together, these models indicate that stress-related behaviors and regulation of voluntary alcohol intake perhaps are among the most important functions of central NPY, and may provide attractive targets for developing novel therapies in depression, anxiety disorders and alcohol dependence.

Neuropeptide Y (NPY) mRNA in rat brain tissue: effects of decapitation and high-energy microwave irradiation on post mortem stability.

mRNA recovery from brain tissue is affected by time-interval from death to inactivation of tissue, and may depend on sacrificial method. Sacrifice by high-energy microwave irradiation increases recovery of intact neuropeptides and proteins, and it has been suggested that this may be valid also for neuropeptide mRNAs. We therefore compared post-mortem NPY mRNA recovery following decapitation or microwave irradiation. Total RNA yield was significantly higher in tissue from decapitated rats. A decline in NPY mRNA (amol/mg tissue) over time, presumably reflecting degradation, was found in frontal cortex, hippocampus and striatum. Following high-energy microwaves, NPY message levels were higher in occipital cortex, lower in the hypothalamus, and unaltered in the other brain regions examined. These results show that post-mortem processes contribute to estimates of NPY mRNA levels obtained using standard methods for obtaining brain tissue from experimental animals and raise the question whether different pools of NPY mRNA might be differentially affected by post-mortem degradation. A general protective effect of high-energy radiation against degradation is not supported.

Decreased experimental anxiety and voluntary ethanol consumption in rats following central but not basolateral amygdala lesions.

A long-debated 'tension reduction' hypothesis postulates anti-anxiety effects to be important for ethanol reward, and states that elevated anxiety levels might predispose for ethanol consumption and addiction. Human data are contradictory, possibly due to heterogeneity of patient samples. In rats, baseline levels of experimental anxiety have been reported to correlate with voluntary ethanol consumption. Here, we addressed the possibility that mechanisms underlying experimental anxiety might be causally related to regulation of voluntary ethanol intake. Rats were bilaterally lesioned in central amygdala using microinjections of ibotenic acid. This resulted in a robust release of punished drinking in a modified Vogel conflict test, an effect typically seen with anxiety reducing drugs. This effect was specific, as unpunished drinking was unaffected by the lesion. On the elevated plus-maze, central amygdala lesions did not affect behaviour under baseline conditions, but attenuated the anxiogenic effect of restraint stress. Measures of locomotor activity were not affected. Voluntary ethanol consumption was examined in a two-bottle, free choice paradigm. Ethanol intake was markedly decreased in the lesion group. Total fluid intake was not affected. Basolateral amygdala lesions, which did not affect conflict behaviour, also left ethanol intake unaffected. These results are consistent with previous reports of an important role for central amygdala in anxiety related behaviours, and suggest that cell bodies located in central amygdala might be important in this context. Further, our results support a relation between experimental anxiety and voluntary ethanol consumption.

Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats.

Activation of central neuropeptide Y (NPY) receptors is known to produce several behavioral effects, including feeding, modulation of memory and antagonism of behavioral effects of stress. In addition, experiments in knock-out and transgenic mice have suggested a possible role of NPY regulation of voluntary ethanol intake. NPY receptors involved in this action are not known. Here, we examined the effects of a selective NPY-Y2 receptor antagonist, BIIE0246, on operant responding for ethanol in a sweetened solution, or the sweetened solution without ethanol, during 30 min sessions of free choice between the two. BIIE0246 produced a robust suppression of responding for ethanol (40% reduction, P=0.013) at an intracerebroventricular dose of 1.0 nmol, but not 0.3 nmol. Responding for the saccharin solution was not significantly affected. The dose range examined was selected since preliminary experiments with doses of 3 nmol and higher indicated sedative effects, but such effects were absent up to 1.0 nmol, as shown by unaffected exploratory locomotor activity. In summary, antagonism at central NPY-Y2 receptors seems to selectively suppress operant self-administration of ethanol. This suggests that Y2 receptors might be candidate targets for developing novel pharmacological treatments of alcoholism.

Leptin suppression of hypothalamic NPY expression and feeding, but not amygdala NPY expression and experimental anxiety.

Leptin decreases food intake through actions in the hypothalamus, partly through interactions with neuropeptide Y (NPY). However, NPY also produces behavioral antistress effects mediated inter alia through the amygdala. If leptin generally suppresses NPY function, the utility of leptin-mimics for treatment of obesity might be limited. Here, we therefore compared the effects of intracerebroventricular leptin on hypothalamic and amygdala NPY expression, as well as the respective related behaviors, i.e., feeding and experimental anxiety. Rats were injected intracerebroventricularly with leptin once daily for 6 days. Leptin-treated subjects consumed significantly less chow and had reduced body weight at the end of the treatment period compared to saline-treated controls. This was accompanied by a significant suppression of hypothalamic NPY expression. In contrast, the expression of NPY within the amygdala was unaffected by leptin. In parallel, in an established animal model of anxiety, the elevated plus-maze, no effect of leptin on anxiety-related behaviors was observed. In conclusion, leptin selectively affects the hypothalamic NPY system and its functional outflow, i.e., feeding and endocrine stress responses. Despite modifying endocrine responses, leptin treatment does not affect behavioral measures of experimental anxiety.

Continuous glucose monitoring: a stepping stone in the journey towards a cure for diabetes.

Probably the most important advance in the field of diabetes and pregnancy since the discovery of insulin in 1921 is self-monitoring of blood glucose. Within the past 30 years, home monitoring of blood glucose has introduced a more efficient means of tracking patient progress. The advent of continuous glucose monitoring has broadened the horizons for improving patient care. Barriers to intensive therapy such as standard methods of monitoring blood glucose, the risk of hypoglycemia, the limitations of present therapy and inadequate patient education must be overcome in order to improve diabetes management. This paper discusses methods of blood glucose monitoring and its aims at bringing the above mentioned barriers to a minimum in order to maintain normoglycemia, to reduce risks of diabetes-related complications and to optimize the possibility for pregnant women with diabetes of delivering healthy babies.