Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

The nature of co-morbid psychopathology in adolescents with gender dysphoria.

Gender-referred adolescents (GR) have been reported to present with considerable psychiatric symptomatology compared to their age-peers. There is, however, little research on how they compare to adolescents referred due to mental health problems (MHR). We set out to compare psychopathology in adolescents referred to our specialized gender identity unit (n = 84) and adolescents referred to a general adolescent psychiatric clinic (n = 293) in a university hospital setting in Finland. Of the GR adolescents, 40.9% had not received any psychiatric diagnosis during adolescence. Eating disorders were less common in the GR than in the MHR group, but otherwise the prevalences of disorders did not differ statistically significantly. At the symptom level, the GR adolescents displayed significantly more suicidal ideation and talk and less alcohol abuse and eating disorder symptoms than did the MHR adolescents, but otherwise their symptom profiles were comparable. Additionally, the GR adolescents had significantly fewer total externalizing symptoms than did the MHR adolescents. Adolescents seeking gender affirming treatments present with psychiatric symptoms and disorders comparable to those seen among adolescent psychiatric patients. Medical gender affirming care may not be a sufficient intervention for treating psychiatric comorbidities of adolescents with gender dysphoria.

Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels.

High serum levels of total and LDL cholesterol are important risk factors in the development of atherosclerotic coronary artery disease. Cholesterol metabolism is affected by nutritional, environmental and genetic factors. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in the hypothalamic regulation of energy balance by stimulating food intake and favoring energy storage through increased lipoprotein lipase activity in white adipose tissue. As a part of ongoing study of the genetic basis of obesity, we screened the NPY gene for sequence variants. We report here the identification of a common Leu(7)-to-Pro(7) polymorphism in the signal peptide of NPY. Presence of this Pro(7) in NPY was associated with higher serum levels of total and LDL cholesterol in obese subjects participating in two independent Finnish and Dutch studies. Furthermore, normal-weight Finns with Pro(7) also had higher serum levels of total and LDL cholesterol than did subjects with Leu(7)/Leu(7), as analyzed in three subsequent determinations at 5-year intervals during a 10-year follow-up period. The NPY polymorphism was not associated with higher cholesterol levels in normal-weight Dutch. Our study provides evidence that NPY is linked to cholesterol metabolism and that the polymorphism producing Pro(7) in NPY is one of the strongest genetic factors identified thus far affecting serum cholesterol, particularly in obese subjects.

Childhood BMI trajectories and the risk of developing young adult-onset diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of childhood BMI growth dynamics on the risk of developing young adult-onset type 1 and type 2 diabetes. METHODS: Finnish national healthcare registers were used to identify individuals with diabetes diagnosed between 1992 and 1996 at 15-39 years of age. Non-diabetic control participants were chosen from the National Population Registry. Anthropometric measurements were obtained from the original child welfare clinic records. Only the case-control pairs with sufficient growth data recorded were included in the analyses (218/1,388 for type 1 diabetes [16%] and 64/1,121 for type 2 diabetes [6%]). Two developmental stages in BMI growth (the points of infancy maximum BMI and the BMI rebound) were examined, and conditional logistic regression was applied to the variables of interest. RESULTS: The risk for type 1 diabetes increased 1.19-fold per 1 kg/m(2) rise in the infancy maximum BMI (p = 0.02). In addition, there was a 1.77-fold increase in the risk for type 2 diabetes per 1 kg/m(2) rise in the level of BMI at the BMI rebound (p = 0.04). Higher values of BMI at these points corresponded to a larger BMI gain from birth to that developmental stage. Age at the infancy maximum BMI or age at the BMI rebound did not affect the risk for either type of diabetes. CONCLUSIONS/INTERPRETATION: The BMI gain in infancy among individuals who subsequently developed young adult-onset type 1 diabetes was faster than that of those who remained healthy. The excess BMI gain in individuals who developed young adult-onset type 2 diabetes could already be seen during early childhood.

Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide.

AIMS: To determine if there is a worldwide seasonal pattern in the clinical onset of Type 1 diabetes. METHODS: Analysis of the seasonality in diagnosis of Type 1 diabetes was based on the incidence data in 0- to 14-year-old children collected by the World Health Organization Diabetes Mondiale (WHO DiaMond) Project over the period 1990-1999. One hundred and five centres from 53 countries worldwide provided enough data for the seasonality analysis. The incidence seasonality patterns were also determined for age- and sex-specific groups. RESULTS: Forty-two out of 105 centres exhibited significant seasonality in the incidence of Type 1 diabetes (P < 0.05). The existence of significant seasonal patterns correlated with higher level of incidence and of the average yearly counts. The correlation disappeared after adjustment for latitude. Twenty-eight of those centres had peaks in October to January and 33 had troughs in June to August. Two out of the four centres with significant seasonality in the southern hemisphere demonstrated a different pattern with a peak in July to September and a trough in January to March. CONCLUSIONS: The seasonality of the incidence of Type 1 diabetes mellitus in children under 15 years of age is a real phenomenon, as was reported previously and as is now demonstrated by this large standardized study. The seasonality pattern appears to be dependent on the geographical position, at least as far as the northern/southern hemisphere dichotomy is concerned. However, more data are needed on the populations living below the 30th parallel north in order to complete the picture.

Impact of the Leu7Pro polymorphism of preproNPY on diurnal NPY and hormone secretion in type 2 diabetes.

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g. circulation, hormone release and angiogenesis. Earlier studies have shown that the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with increased risk for vascular complications in type 2 diabetes. The mechanism for this maybe altered transmitter and hormone levels or altered cardiovascular functions, which have been observed in healthy subjects having the Leu7Pro polymorphism. The current study was undertaken to explore if the Leu7Pro polymorphism has an impact on these functions in subjects with type 2 diabetes. Diurnal measurements were performed for Finnish Caucasian type 2 diabetes patients of two preproNPY genotypes (matched by sex, age, BMI, duration of diabetes and HbA1c) in resting position to prevent sympathetic stimulation. Standard meals were offered during the 24-hour study period. Nine subjects with the Leu7Pro polymorphism and ten subjects without this polymorphism were studied. Plasma concentrations of NPY, glucose, insulin, cortisol, prolactin and leptin were measured by taking blood samples at 20 time points (from 8 a.m. to 8 a.m.). Heart rate and blood pressure were measured at the same time points. The results show that NPY concentrations were similar in both preproNPY genotypes. Glucose, insulin, cortisol and leptin concentrations as well as heart rate and blood pressure were also similar. However, a significant difference between genotypes was found in the association of NPY concentrations with cortisol concentrations (p for difference=0.002). Also a statistically significant negative association of plasma NPY levels with plasma glucose levels was found in both genotypes. Since no impact of preproNPY genotype on mean NPY or hormone levels were detected in subjects with type 2 diabetes, the mechanisms for the increased risk for diabetic complications in the subjects with the Leu7Pro polymorphism need to be further explored.

Freedom Constrained Liner for the Treatment and Prevention of Dislocation in Total Hip Arthroplasty.

BACKGROUND AND PURPOSE: Dislocation is one of the most common complications following total hip arthroplasty. The aim of our study was to assess failure rate of the Biomet Freedom constrained liner (Biomet, Warsaw, IN, USA) either in revision surgery for recurrent dislocation, or as a preventive method in high dislocation risk patients. PATIENTS AND METHODS: We assessed retrospectively 105 consecutive surgical procedures in 103 patients where a Freedom constrained liner or cup was used in Turku University Hospital over a 7-year period from 2007 to 2014. The mechanical failure rate of the device was assessed based on medical records. The average age of the patients was 73.4 years. The number of male patients was 53 (51%). Mean follow-up time was 2.5 years. The association between failure of the device and potential risk factors-age, gender, indication, and approach-was analyzed with logistic regression. Results were expressed by odd ratios and 95% confidence intervals. RESULTS: The mechanical failure rate of the Freedom device was 6 out of 105 (5.7%). None of the 11 preventive primary THAs against dislocation failed, 4 out of 52 (7.7%) preventive revision THAs against dislocation failed, and 2 out of 42 (4.8%) of the treated dislocation cases failed. Four out of six failures were dislocations due to impingement and failure of the locking mechanism. Two liners failed because of loosening. The risk factors assessed were not associated with failure of the device. INTERPRETATION: We found out that the mechanical failure rate of a Freedom constrained device was low. These results encourage us to continue using the device.

An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events.

OBJECTIVES: Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases. BACKGROUND: alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction. METHODS: This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years. RESULTS: In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population. CONCLUSIONS: The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Serum cholesterol and risk of accidental or violent death in a 25-year follow-up. The Finnish cohorts of the Seven Countries Study.

In the two most recent cholesterol-lowering drug trials, the achieved reductions in coronary heart disease mortality were offset by increases in mortality due to accidents and violence. A possible biochemical explanation has been suggested for an association between low serum cholesterol level and increased risk of death due to injury. We, therefore, examined the association between serum cholesterol level and risk of death from accidents or violence in the 25-year follow-up of two cohorts of Finnish men (N = 1580). Although a statistically nonsignificant, negative association was observed in one cohort (hazard ratio, 0.84, with a 1 mmol/L increase in cholesterol), the other cohort showed a statistically significant, positive association in multivariate analysis (hazard ratio, 1.39). We conclude that the observed associations between serum cholesterol and deaths from injury in the present study and in cholesterol-lowering trials are probably determined by other, presently unknown factors, or by chance.

The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group.

OBJECTIVE: To analyze the change in the age distribution at onset of type 1 diabetes in boys and girls aged 1-14 years during a 32-year period (from 1965 to 1996). RESEARCH DESIGN AND METHODS: Data on the incidence of type 1 diabetes in Finland were obtained from the Central Drug Registry of the Social Insurance Institution for 1965-1986 (6,195 cases) and from the Prospective Childhood Diabetes Registry for 1987-1996 (3,613 cases). The change in age- and sex-specific incidence was estimated by fitting the linear regression with the logarithm of the annual incidence data. Analysis of variance was used to compare the trends between the various age-groups (1-4, 5-9, and 10-14 years) and sexes. RESULTS: The incidence of type 1 diabetes increased predominantly in the younger age-groups. In children aged 1-4 years, the increase was 4.2% per year, and the overall 32-year relative increase was 338%. For children aged 5-9 and 10-14 years, the increase was 2.5 and 1.3% per year, respectively, and the overall relative increase was 116 and 49%, respectively. In boys aged 1-9 years, the increase was greatest from 1965 to 1984, whereas in girls aged 1-9 years, the statistically significant increase occurred between 1985 and 1996. In children aged 10-14 years, the only significant increase was seen in boys from 1965 to 1974 (3.7% per year). CONCLUSIONS: The greatest increase in the incidence of type 1 diabetes mainly occurred in children aged < 5 years. The incidence in young boys has been increasing since the mid-1960s, whereas in young girls, the significant increase began later, around the mid-1970s. In children aged 10-14 years, the increase in incidence has leveled off.

Comparison of the seasonal pattern in the clinical onset of IDDM in Finland and Sardinia.

OBJECTIVE: To examine the seasonal pattern for the clinical onset of IDDM in Finland and Sardinia, two areas where the incidence of IDDM is the highest in the world, and to determine the effect of climate and temperature on the clinical onset of IDDM. RESEARCH DESIGN AND METHODS: Analysis of seasonality for the diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardinia diagnosed at < or = 14 years of age from 1989 to 1992. The average annual incidence of IDDM was 36.4/100,000 in Finland and 34.4/100,000 in Sardinia. Seasonal patterns were estimated presenting the data as short Fourier series up to three harmonics together with a possible linear trend. Likelihood ratio tests and Akaike's information criterion were used to determine the number of harmonics necessary to model the seasonal pattern. Seasonal patterns in both countries were compared between sexes and between the three 5-year age-groups, each controlling for the other's effect. RESULTS: In both countries, a significant seasonal pattern during a calendar year was found for the sexes combined and for two age-groups (0-9 and 10-14 years). In Sardinia, two distinct cycles were found in the younger age-group, with a decreased incidence during May through August and an increased incidence during the autumn months. Two cycles were apparent in the older age-group, with the nadir occurring during June through September. In Finland, one cycle was found in the younger age-group, with a decreased incidence in June. In the older age-group, there were two distinct cycles, with a decreased incidence in June and in the September through December period. CONCLUSIONS: Differences between Finland and Sardinia in the seasonal pattern for the incidence of newly diagnosed IDDM cannot be explained by differences in climate, temperature, a longer warm period in Sardinia, or other climatic phenomena. The results do not provide evidence in favor of a specific viral etiology of IDDM. It may be suggested that there are triggering events at certain times, but they are likely to be unspecific. Nevertheless, why the incidence of IDDM in these two populations is equally high despite differences in climate, environment, and genetic background remains an unsolved question.

Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group.

OBJECTIVE: To investigate and monitor the patterns in incidence of childhood type 1 diabetes worldwide. RESEARCH DESIGN AND METHODS: The incidence of type 1 diabetes (per 100,000 per year) from 1990 to 1994 was determined in children < or =14 years of age from 100 centers in 50 countries. A total of 19,164 cases were diagnosed in study populations totaling 75.1 million children. The annual incidence rates were calculated per 100,000 population. RESULTS: The overall age-adjusted incidence of type 1 diabetes varied from 0.1/100,000 per year in China and Venezuela to 36.8/100,000 per year in Sardinia and 36.5/100,000 per year in Finland. This represents a >350-fold variation in the incidence among the 100 populations worldwide. The global pattern of variation in incidence was evaluated by arbitrarily grouping the populations with a very low (<1/100,000 per year), a low (1-4.99/100,000 per year), an intermediate (5-9.99/100,000 per year), a high (10-19.99/100,000 per year), and a very high (> or =20/100,000 per year) incidence. Of the European populations, 18 of 39 had an intermediate incidence, and the remainder had a high or very high incidence. A very high incidence (> or =20/ 100,000 per year) was found in Sardinia, Finland, Sweden, Norway Portugal, the U.K., Canada, and New Zealand. The lowest incidence (<1/100,000 per year) was found in the populations from China and South America. In most populations, the incidence increased with age and was the highest among children 10-14 years of age. CONCLUSIONS: The range of global variation in the incidence of childhood type 1 diabetes is even larger than previously described. The earlier reported polar-equatorial gradient in the incidence does not seem to be as strong as previously assumed, but the variation seems to follow ethnic and racial distribution in the world population.

Mortality in patients with childhood-onset type 1 diabetes in Finland, Estonia, and Lithuania: follow-up of nationwide cohorts.

OBJECTIVE: To assess mortality of population-based cohorts of childhood-onset type 1 diabetic patients from the Eastern European countries of Estonia and Lithuania and compare this information with recent data from Finland. RESEARCH DESIGN AND METHODS: Estonian (n = 518) and Finnish (n = 5,156) type 1 diabetic cohorts were diagnosed between 1980 and 1994, and the Lithuanian (n = 698) cohort was diagnosed between 1983 and 1994. The mortality of these cohorts was determined in 1995. Life-table analysis, Cox survival analysis with covariates, and standardized mortality ratios (SMRs) were used. Causes of death were analyzed. RESULTS: Survival after 10 years duration of type 1 diabetes was similar in Estonia (94.3%) and Lithuania (94.0%), but much higher in Finland (99.1%). In the Cox survival analysis with covariates, the country of origin and age at diagnosis were found to be significant predictors of mortality. The SMR for the Estonian cohort was 4.35 (95% CI 2.25-7.61), the highest for the Lithuanian cohort was 7.55 (4.89-11.15), and the lowest for the Finnish cohort was 1.62 (1.10-2.28). The most common cause of death in Estonia and Lithuania was diabetic ketoacidosis (DKA), and in Finland, it was violent causes. No deaths from late complications of diabetes have been documented so far in any of the three countries. CONCLUSIONS: Our results demonstrate a high rate of short-term deaths due to DKA and inferior survival of childhood-onset type 1 diabetic patients in Estonia and Lithuania compared with Finland. In Finland, the survival of childhood-onset type 1 diabetic patients has improved and is only slightly inferior to that of the background population.

Incidence of IDDM in Mauritian children and adolescents from 1986 to 1990.

OBJECTIVE: To document the incidence of IDDM in Mauritian children and adolescents 0-19 yr of age from 1986 to 1990. RESEARCH DESIGN AND METHODS: We used a population-based register that used pediatricians, physicians, nutritionists, and general practitioners as a primary source of retrospective case ascertainment. The denominator data were obtained from the Statistics Office of the Ministry of Health (Port Louis, Mauritius). RESULTS: In 1990, 37 newly diagnosed IDDM cases (22 females and 15 males) were identified between 1986 and 1990 among the population < or = 19 yr of age. The average incidence density per year was 1.9/100,000 people and was slightly higher among girls (2.2/100,000) than among boys (1.5/100,000). The average age-standardized incidence density was 2.1/100,000 people (95% confidence interval 1.5-3.0) among children < or = 14 yr of age, 2.5/100,000 people (95% confidence interval 1.5-3.9) among girls, and 1.8/100,000 people (95% confidence interval 1.0-3.0) among boys. The incidence was similarly low in Mauritians of Asian Indian, Chinese, and Creole (predominantly African) origin. CONCLUSIONS: The incidence of IDDM in Mauritian children and adolescents is among the lowest yet reported. This sharply contrasts with the very high risk of NIDDM found among the adult population in this rapidly modernizing country.

Enhanced exercise-induced GH secretion in subjects with Pro7 substitution in the prepro-NPY.

The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of NPY is associated with high blood lipid concentrations and accelerated rate of atherosclerosis as well as diabetic retinopathy. Also, healthy subjects with this polymorphism have increased NPY secretion during sympathetic stimulation. Because NPY may regulate GH release and ghrelin may regulate NPY formation, we studied the effects of the Leu7/Pro7 genotype on GH, ghrelin, and IGF-I secretion during standardized cycle-ergometer exercise. Furthermore, we studied the effect of the Leu7/Pro7 genotype on diurnal GH secretion in rest in a separate study. The subjects with Leu7/Pro7 genotype had 54% higher maximal increases in the plasma GH concentrations than the controls during exercise. There were no significant differences in the ghrelin or IGF-I concentrations during exercise among the groups. Furthermore, there were no differences in diurnal GH secretion between the genotypes. The results indicate that the prepro-NPY genotype has an influence on GH response during exercise in humans. The clinical significance of this finding is not known, and further studies are needed to evaluate whether the observed change in GH secretion during exercise could play a role in promoting diseases.

Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects.

The alpha2-adrenergic receptors mediate part of the actions of the catecholamines noradrenaline and adrenaline on the regulation of energy balance. As part of an ongoing study on the genetics of obesity, the entire coding sequence of the alpha2B-adrenoceptor gene was screened in 58 obese, nondiabetic Finns by PCR-single stranded conformational analysis (PCR-SSCA). A polymorphism that leads to a deletion of 3 glutamic acids from a glutamic acid repeat element (Glu x 12, amino acids 297-309) present in the third intracellular loop of the receptor protein was identified. This repeat element has previously been shown to be important for agonist-dependent receptor desensitization. Of 166 genotyped subjects, 47 (28%) had 2 normal (long) alleles (Glu12/Glu12), 90 (54%) were heterozygous (Glu12/Glu9), and 29 (17%) were homozygous for the short (Glu9/Glu9) form. The basal metabolic rate, determined by indirect calorimetry and adjusted for fat-free body mass, fat mass, sex, and age, was 94 Cal/day (5.6%) lower (95% confidence interval for difference, 32, 156) in subjects homozygous for the short allele than in subjects with two long alleles (F = 4.84; P = 0.009, by ANOVA). Thus, a genetic polymorphism of the alpha2B-adrenoceptor subtype can partly explain the variation in basal metabolic rate in an obese population and may therefore contribute to the pathogenesis of obesity.

Leucine 7 to proline 7 polymorphism in the preproneuropeptide Y is associated with birth weight and serum triglyceride concentration in preschool aged children.

The Leu7Pro gene variant of the signal peptide part of neuropeptide Y (NPY), has been shown to affect cholesterol metabolism in obese adults. This study investigates whether the Leu7Pro polymorphism in the prepro-NPY has an impact on serum lipid concentrations in preschool-aged children at 5 and 7 yr of age. As birth weight may influence future lipid values, we also investigated whether Leu7Pro polymorphism is associated with birth weight. The study comprised 688 children participating in the Special Turku Coronary Risk Factor Intervention Project. Fasting lipid concentrations were determined first at the age of 5 yr and again at the age of 7 yr. The Leu7Pro polymorphism was not associated with serum total or low density lipoprotein cholesterol values in boys or in girls. However, Pro7 substitution in prepro-NPY was constantly associated with 14-17% higher mean serum triglyceride values in the boys at the ages of 5 and 7 yr (P = 0.023). In addition, boys with the Pro7 substitution had, on the average, a 193-g higher birth weight than boys homozygous for Leu7 (P = 0.03). The Leu7Pro polymorphism may thus be linked with serum triglyceride concentrations, but not with serum cholesterol concentrations, in gender-specific manner in preschoolers.

Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects.

We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.