Charlotta Pisinger

A systematic review of health effects of electronic cigarettes.

OBJECTIVEnTo provide a systematic review of the existing literature on health consequences of vaporing of electronic cigarettes (ECs).nnnMETHODSnSearch in: PubMed, EMBASE and CINAHL.nnnINCLUSION CRITERIAnOriginal publications describing a health-related topic, published before 14 August 2014. PRISMA recommendations were followed. We identified 1101 studies; 271 relevant after screening; 94 eligible.nnnRESULTSnWe included 76 studies investigating content of fluid/vapor of ECs, reports on adverse events and human and animal experimental studies. Serious methodological problems were identified. In 34% of the articles the authors had a conflict of interest. Studies found fine/ultrafine particles, harmful metals, carcinogenic tobacco-specific nitrosamines, volatile organic compounds, carcinogenic carbonyls (some in high but most in low/trace concentrations), cytotoxicity and changed gene expression. Of special concern are compounds not found in conventional cigarettes, e.g. propylene glycol. Experimental studies found increased airway resistance after short-term exposure. Reports on short-term adverse events were often flawed by selection bias.nnnCONCLUSIONSnDue to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of ECs. However, they can hardly be considered harmless.

Association of obesity and insulin resistance with asthma and aeroallergen sensitization.

Background: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization.

Insulin resistance as a predictor of incident asthma-like symptoms in adults.

Background There is accumulating evidence that obesity is associated with an increased risk of asthma. It has been hypothesized that insulin resistance may be involved in obesity‐induced asthma, but till date there is no prospective data on this issue.

Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes

Aims/hypothesisWe studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237).MethodsInformation about size at birth and prematurity was identified from original midwife records in 4,744 middle-aged Danes. Type 2 diabetes status, insulin sensitivity (Matsuda index) and beta cell function (disposition index) were assessed using a 75xa0g oral glucose tolerance test. Participants born prematurely were compared with a group of at-term participants born small for gestational age.ResultsAn increase in birthweight of 1xa0kg was associated with a 51% (OR 0.49, 95% CI 0.35–0.69) reduced risk of type 2 diabetes. Ponderal index, reflecting thinness at birth, was associated with type 2 diabetes to the same extent as birthweight. The prevalence of type 2 diabetes was increased to a similar degree in participants born prematurely and participants born small for gestational age, although the former had a higher ponderal index at birth. In addition, birthweight z-scores, reflecting fetal growth rate, were unrelated to the risk of type 2 diabetes and to other measures of glucose regulation in participants born prematurely. While low birthweight was inversely associated with insulin sensitivity and beta cell function, prematurity was associated solely with decreased insulin sensitivity.Conclusions/interpretationWhile the association between birthweight and risk of type 2 diabetes is mediated via combined effects on beta cell function and insulin sensitivity, prematurity seems to influence risk of type 2 diabetes via attenuated insulin sensitivity only and independently of fetal growth rates.

Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight

Aims/hypothesisThe fetal insulin hypothesis suggests that variation in the fetal genotype influencing insulin secretion or action may predispose to low birthweight and type 2 diabetes. We examined associations between 25 confirmed type 2 diabetes risk variants and birthweight in individuals from the Danish Inter99 population and in meta-analyses including Inter99 data and reported studies.MethodsMidwife records from the Danish State Archives provided information on mother’s age and parity, as well as birthweight, length at birth and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. We genotyped 25 risk alleles showing genome-wide associations with type 2 diabetes.ResultsBirthweight was inversely associated with the type 2 diabetes risk alleles of ADCY5 rs11708067 (βu2009=u2009−33xa0g [95% CI −55, −10], pu2009=u20090.004) and CDKAL1 rs7756992 (βu2009=u2009−22xa0g [95% CI −43, −1], pu2009=u20090.04). The association for the latter locus was confirmed in a meta-analysis (nu2009=u200924,885) (βu2009=u2009−20xa0g [95% CI −29, −11], pu2009=u20095u2009×u200910−6). The HHEX-IDE rs1111875 variant showed no significant association among Danes (pu2009=u20090.09); however, in a meta-analysis (nu2009=u200925,164) this type 2 diabetes risk allele was associated with lower birthweight (βu2009=u2009−16xa0g [95% CI −24, −8], pu2009=u20098u2009×u200910−5). On average, individuals with high genetic risk (≥25 type 2 diabetes risk alleles) weighed marginally less at birth than those with low genetic risk (<25 type 2 diabetes risk alleles) (βu2009=u2009−35xa0g [95% CI −69, −2], pu2009=u20090.037).Conclusions/interpretationWe report a novel association between the fetal ADCY5 type 2 diabetes risk allele and decreased birthweight, and confirm in meta-analyses associations between decreased birthweight and the type 2 diabetes risk alleles of HHEX-IDE and CDKAL1. No strong general effect on birthweight can be ascribed to the 25 common type 2 diabetes risk alleles.

Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study

Low vitamin D status has been associated with cardiovascular disease (CVD) and mortality primarily in selected groups, smaller studies, or with self-reported vitamin D intake. We investigated the association of serum vitamin D status with the incidence of a registry-based diagnosis of ischemic heart disease (IHD), stroke, and all-cause mortality in a large sample of the general population. A total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, were included. Measurements of serum 25-hydroxyvitamin D at baseline were carried out using the IDS ISYS immunoassay system in Monica10 and High-performance liquid chromatography in Inter99. Information on CVDs and causes of death was obtained from Danish registries until 31 December 2008. There were 478 cases of IHD, 316 cases of stroke, and 633 deaths during follow-up (mean follow-up 10xa0years). Cox regression analyses with age as underlying time axis showed a significant association between vitamin D status and all-cause mortality with a HRxa0=xa00.95 (Pxa0=xa00.005) per 10xa0nmol/l higher vitamin D level. We found no association between vitamin D status and incidence of IHD or stroke (HRxa0=xa01.01, Pxa0=xa00.442 and HRxa0=xa01.00, Pxa0=xa00.920, respectively). In this large general population study, the observed inverse association between serum vitamin D status and all-cause mortality was not explained by a similar inverse association with IHD or stroke.

Vitamin D status and cause-specific mortality: a general population study.

Background Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality. Methods We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years). Results Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (ptrendu200a=u200a0.0042), 0.28 (ptrendu200a=u200a0.0040), and 0.21 (ptrendu200a=u200a0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system. Conclusion The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.

Vitamin D Status, Filaggrin Genotype, and Cardiovascular Risk Factors: A Mendelian Randomization Approach

Background Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. Methods Three population based studies were included, Monica10 (2,656 individuals aged 40–71 years), Inter99 (6,784 individuals aged 30–60 years), and Health2006 (3,471 individuals aged 18–69 years) conducted in 1993–94, 1999–2001, and 2006–2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. Results Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratiou200a=u200a0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. Conclusion Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study

Vitamin D deficiency is common among patients with liver diseases. Both cholestatic and non-cholestatic liver diseases can cause vitamin D deficiency. Whether vitamin D status can also affect liver function is poorly understood. To investigate the association between vitamin D status, liver enzymes, and incident liver disease, we included a total of 2,649 individuals from the Monica10 study conducted in 1993–1994. Vitamin D status as assessed by serum 25-hydroxyvitamin, serum alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were measured at baseline. Information on fatal and non-fatal liver disease was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death, respectively. Median follow-up time was 16.5xa0years, and there were 62 incident cases of fatal and non-fatal liver disease. Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed a statistically significant inverse association between vitamin D status and incident liver disease with a hazard ratioxa0=xa00.88 (95xa0% confidence interval 0.79–0.99) per 10xa0nmol/l higher vitamin D status at baseline (adjusted for gender, season, alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes.

Why public health people are more worried than excited over e-cigarettes

The research field on e-cigarettes is characterized by severe methodological problems, severe conflicts of interest, relatively few and often small studies, inconsistencies and contradictions in results, and a lack of long-term follow-up. Therefore, no firm conclusions can be drawn on the harm of e-cigarettes, but they can hardly be called safe. Experimental studies indicate negative health effects and, amongst others, the major ingredient propylene glycol warrants concern. Growing evidence raises doubt about the efficacy of e-cigarettes as a smoking cessation aid. Unfortunately, it seems that many smokers use e-cigarettes with the intention to quit but switch to long-term use of e-cigarettes or dual use. Use is spreading rapidly to minors, ex-smokers, and never-smokers. It is questionable whether the potential health benefits obtained by some smokers outweigh the potential harm by use of non-smokers, of undermining of complete cessation, smokers’ dual use, and of eventual re-normalization of smoking. Even if e-cigarettes are significantly less harmful than conventional cigarettes, the product may have a very negative impact on public health if its use is spread to a large part of the population.