Low serum adiponectin levels in childhood and adolescence predict increased intima-media thickness in adulthood. The Cardiovascular Risk in Young Finns Study

Introduction: Low adiponectin levels may predict the development of atherosclerosis. We examined the association of childhood adiponectin with preclinical carotid atherosclerosis that is defined as plaque and/or high (≥95th percentile) intima-media thickness (IMT) at the carotid bifurcation in adulthood.

Methods: The Cardiovascular Risk in Young Finns Study is a cohort study on cardiovascular risk factors. We used risk factor data from the baseline study (1980) and ultrasound findings from the follow-ups (2001 and 2007). The study population included 1708 participants, aged 3–18 years at baseline.

Results: In multivariate analysis, childhood adiponectin was inversely associated with preclinical carotid atherosclerosis: odds ratio 0.68, 95% confidence interval (CI) 0.53–0.86, p?=?.001, for 1-SD increase in childhood adiponectin after adjusting for childhood non-high-density lipoprotein cholesterol, body mass index, and blood pressure. When examining the incremental predictive ability, we observed that compared to an approach utilizing only conventional risk factors, the model additionally including adiponectin levels improved c-statistics area under curve from 0.733 (95% Cl 0.694–0.771) to 0.748 (95% Cl 0.710–0.786), p?=?.02.

Conclusions: Childhood adiponectin levels improve the prediction of carotid atherosclerosis in adulthood over conventional risk factors. This supports the idea that low adiponectin levels may have a role in the development of preclinical atherosclerosis.

• Key messages

• Childhood adiponectin levels improve the prediction of increased carotid intima-media thickness in adulthood over conventional cardiovascular risk factors.

• These results suggest that adiponectin levels measured in childhood may have a role in the atherosclerotic process.

     

A follow-up EEG study in diabetic children

498 electroencephalograms (EEGs) were recorded from 195 diabetic children during a follow-up study. The children were divided into stable and labile groups according to diabetes control. The labile group was further subdivided into hypoglycaemic, ketoacidotic and mixed groups. In general it was found that the labile children had significantly more abnormal findings in their EEGs than the stable children, as expected. This applied particularly to generalized discharges with spikes and sharp waves or focal findings, but not to cases with only a diffuse-slowing. Nonstatistical differences in EEG abnormality were seen between the hypoglycaemic and ketoacidotic group--an unexpected finding. During the follow-up the labile group more often had an increasing EEG abnormality than the stable group. For those children who had an EEG abnormality but without an increasing tendency, there was no difference in the EEGs between the labile and stable children. It was concluded tht some of the EEG abnormalities are acquired, and apparently produced by a metabolic disturbance caused by diabetes. However, other causes may be of genetic or perinatal origin, or perhaps a combination of different causes. Because of the multifactorial aetiology of the abnormalities, EEG cannot at present be recommended for routine testing of the effects of metabolic disturbance in diabetics.     

Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population

OBJECTIVE: The gastrointestinal (GI) safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in a real-life setting remains ill defined. The aim of this study was to examine the risk of upper GI events associated with various NSAIDs in a general population. MATERIAL AND METHODS: A nationwide, register-based, matched case-control study was carried out in outpatient residents of Finland in 2000-04. Cases with upper GI events (n=9191) were drawn from the Hospital Discharge Register and individually matched to controls (n=41,780) from the Population Register. RESULTS: The semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, etodolac) had the highest odds ratio for upper GI events even after adjusting for various potential confounders (adjusted odds ratio (AOR) 3.63; 95% CI 3.08-4.28), followed by non-selective (2.98; 2.70-3.29) and COX-2 selective NSAIDs (2.53; 2.09-3.07). When the current use of semi-selective NSAIDs was compared with that of non-selective and COX-2 selective NSAIDs, the AORs were 1.54 (1.13-2.09) and 1.67 (1.10-2.53), respectively. The AORs for the use of COX-2 selective NSAIDs did not differ statistically from the non-selective NSAIDs (AOR 0.92; 0.65-1.31). The AORs for individual NSAIDs varied across and within categories. CONCLUSIONS: As a group, the GI safety of the COX-2 selective NSAIDs was not demonstrated as definitively superior to non-selective NSAIDs. Semi-selective NSAIDs do not seem to offer any GI advantage over other NSAIDs.     

Relationship between leptin and C-reactive protein in young Finnish adults

CONTEXT: Leptin and C-reactive protein (CRP) concentrations are increased in inflammation, and both have been linked to increased risk for cardiovascular diseases. OBJECTIVE: The objective of the study was to explore in a population-based sample whether the relation between leptin and CRP is independent of obesity level and whether genetic causes of CRP elevation contribute to leptin levels. DESIGN: This was a population-based study including 1862 young adults (971 women; 891 men) aged 24-39 yr. SETTING: The study was conducted at five centers in Finland. MAIN OUTCOME MEASURES: Associations between leptin and CRP adjusted for obesity indices, risk factors, genetic variables, and lifestyle variables were measured. RESULTS: Women had 3.0-fold higher median concentrations of leptin (12.5 vs. 4.1 ng/ml) and 1.3-fold higher median concentrations of CRP (0.75 vs. 0.56 mg/liter) than men (P < 0.0001 in both comparisons). In univariate analyses, CRP and leptin were significantly intercorrelated (r = 0.47, P < 0.0001 for women; r = 0.46, P < 0.0001 for men). In multiple regression analysis including age, body mass index, waist circumference, insulin, lipids, systolic and diastolic blood pressures, smoking status, and use of oral contraceptives in women, leptin was the main determinant of CRP in men (P < 0.0001) and the second most important determinant in women (P < 0.0001). A Mendelian randomization test based on genetic variants in the CRP gene (five single nucleotide polymorphisms) provided no support for CRP as a causal agent for leptin. CONCLUSIONS: Leptin, obesity, and oral contraceptive use in women were the main factors related to CRP. The relation between leptin and CRP was independent of obesity and cardiovascular risk factors.     

Improved computational fronto-central sleep depth parameters show differences between apnea patients and control subjects

All-night EEG recordings from 12 male apnea patients and 12 age-matched healthy control subjects were studied in the present work. The spectral mean frequency was used to provide computational sleep depth curves from two frontopolar and two central EEG channels. Our previously presented computational parameters quantifying the properties of the sleep depth curves were improved. The resulting light sleep percentage (LS%) values were higher in apnea patients than in control subjects in the right central brain position (P = 0.028), in concordance to our previous work. Moreover, apnea patients showed higher LS% values in the right frontopolar position (P = 0.008). Also, apnea patients showed a smaller anteroposterior sleep depth difference than control subjects on the right hemisphere (P = 0.002). These are interesting new findings, achieved by the present methodology. Thus, the developed computational parameters were able to quantify, at least to some degree, the disruption of sleep process caused by the recurrent apneic events.     

Diffuse sleep spindles show similar frequency in central and frontopolar positions

The objective of the present work was to examine fronto-central spindle frequency. A previously validated spindle detector, providing an electroencephalographic (EEG) amplitude independent spindle detection, was used to detect bilateral sleep spindles from sleep EEG recordings of ten healthy subjects with a time resolution of 0.33-s. A bilateral spindle detected centrally and frontopolarly simultaneously is called here a diffuse spindle. A bilateral spindle detected only frontopolarly or centrally at a given time is called a pure frontopolar and a pure central spindle, respectively. Spindle frequency was obtained with zero-padded discrete Fourier transform (DFT). Waveform phase angle of diffuse spindles was also examined. A total of 1230 diffuse spindles and 5316 pure central and 2595 pure frontopolar spindles were detected. The difference of median spindle frequency between central and frontopolar brain positions was clearly smaller in diffuse spindles than in pure spindles. Moreover, 34% of the diffuse spindles showed a similar frequency in central and frontopolar locations. This figure was up to 50.9% when including the 700 diffuse spindles fulfilling a strict anteroposterior (AP) timing criteria. The timing criteria selection in diffuse spindle analysis is a new functionality, enabled by the present spindle analysis method. Diffuse spindles showed coherent spindle oscillation in a large fronto-central area. Pure frontopolar spindles might be special cases of diffuse spindles, both of them seem to be generated in the nucleus medialis dorsalis (NMD) of the thalamus.     

Intelligent methods for identifying respiratory cycle phases from tracheal sound signal during sleep

We present two methods for identifying respiratory cycle phases from tracheal sound signal during sleep. The methods utilize the Hilbert transform in envelope extraction. They determine automatically a patient-specific amplitude threshold to be used in the detection. The core of one method is designed to be amplitude-independent whereas the other method uses solely the amplitude information. The methods provided average sensitivities of 98% and 99%, respectively, and positive prediction values of 100% on the total of 1434 respiratory cycles analysed from six different patients. The developed methods seem promising as such or as tools for analysing sleep disordered breathing.     

Improved stability and release control of levodopa and metaraminol using ion-exchange fibers and transdermal iontophoresis

Achievement of controlled drug delivery and stability of drugs during storage is a problem also in transdermal drug delivery. The objective of this study was to determine, whether an easily oxidized drug, levodopa, could be stabilized during storage using pH-adjustment and ion-exchange fibers. Controlled transdermal delivery of the zwitterionic levodopa was attempted by iontophoresis and ion-exchange fiber. Ion-exchange kinetics and transdermal permeation of a cationic (presumably more stable) model drug, metaraminol, were compared to the corresponding data of levodopa. Levodopa was rapidly oxidized in the presence of water, especially at basic pH-values. At acidic pH-values the stability was improved significantly. Ion-exchange group and the pH had a clear effect on the release of both the levodopa and metaraminol from the ion-exchange fiber. The adsorption/release kinetics of metaraminol were more easily controllable than the corresponding rate and extent of levodopa adsorption/release. Iontophoretic enhancement of drug permeation across the skin was clearly more significant with the positively charged metaraminol than with the zwitterionic levodopa. Ion-exchange fibers provide a promising alternative to control drug delivery and to store drugs that are degraded easily.     

Insulin and sulphonylurea in the therapy of type 2 diabetes

The role of insulin in the therapy of NIDDM is still under discussion. To clarify the problem we performed a randomized double-blind placebo controlled crossover study of insulin treatment for 4 weeks in diabetic patients (n = 18, age 52-74 years) who were unsatisfactorily controlled by oral antidiabetic agents. The patients continued to use these agents during the study. Special attention was given to informing the patients about the trial and, in particular, about self-monitoring the blood glucose by the use of a reflectance meter. Insulin treatment produced the following significant changes: decreases in blood glucose (at 7.00, 10.00, 16.00), mean daily blood glucose, HbA1, urinary glucose and low density lipoprotein (LDL) cholesterol and increased postglucose immunoreactive insulin (IRI) levels. Significant changes were also observed during the placebo periods: decreases in HbA1 urinary glucose and LDL cholesterol (but not in blood glucose). Therapy with insulin increased the body weight, whereas the placebo insulin had the opposite effect. The finding emphasizes the importance of using not only a run-in period but also a placebo design when the metabolic effects of antidiabetes therapy are to be evaluated. The study indicates that insulin therapy for patients with type 2 diabetes can be initiated at home.