Trends in Overweight and Obesity among Children and Adolescents in China from 1981 to 2010: A Meta-Analysis

Background

Overweight/obesity is a serious public health problem that affects a large part of the world population across all age and racial/ethnic groups. However, there has not been a meta-analysis of the prevalence of childhood and adolescent overweight/obesity in China during the past 30 years.

Methods

The China National Knowledge Infrastructure and Wanfang DATA, MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature were searched for relevant studies published between January 1970 and June 2012. The prevalence of overweight/obesity over time was pooled using Stata/SE, version 9. Summary statistics (odds ratios, ORs) were used to compare sex-specific and urban-rural preponderance of overweight/obesity using Review Manager.

Results

After screening 1326 papers, we included 35 papers (41 studies), most of medium quality. The prevalence of overweight/obesity increased from 1.8% (95% confidence interval [CI], 0.4%–3.1%) and 0.4% (95% CI, −0.1% to −0.8%) respectively in 1981–1985 to 13.1% (95% CI, 11.2%–15.0%) and 7.5% (95% CI, 6.6%–8.4%) respectively in 2006–2010. The average annual increase was 8.3% and 12.4% respectively. Boys were more likely to be overweight/obese than girls (OR, 1.36; 95% CI, 1.24–1.49 and OR, 1.68; 95% CI, 1.52–1.86 respectively). The prevalence of overweight/obesity was higher in urban areas than in rural areas (OR, 1.66; 95% CI, 1.54–1.79 and OR, 1.97; 95% CI, 1.68–2.30 respectively). For age-specific subgroup analyses, both overweight and obesity increased more rapidly in the toddler stage than in other developmental stages. Sensitivity analyses showed that sample-size differences, study quality, overweight/obesity criteria and geographical distribution affected overweight/obesity prevalence.

Conclusions

Toddlers and urban boys were at particularly high risk; the prevalence in these groups increased more rapidly than in their counterparts. Public health prevention strategies are urgently needed to modify health behaviors of children and adolescents and control overweight/obesity in China.     

The FTO Gene rs9939609 Polymorphism Predicts Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

Objective

Genome-wide association studies have shown that variance in the fat mass- and obesity- associated gene (FTO) is associated with risk of obesity in Europeans and Asians. Since obesity is associated with an increased risk of cardiovascular disease (CVD), several studies have investigated the association between variant in the FTO gene and CVD risk, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of rs9939609 variant (or its proxies [r ²>0.90]) in the FTO gene with CVD risk.

Methods

Published literature from PubMed and Embase was retrieved. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random- effects model.

Results

A total of 10 studies (comprising 19,153 CVD cases and 103,720 controls) were included in the meta-analysis. The results indicated that the rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18, 95% confidence interval = 1.07–1.30, p = 0.001 [Z test], I ² = 80.6%, p<0.001 [heterogeneity]), and there was an insignificant change after adjustment for body mass index (BMI) and other conventional CVD risk factors (odds ratio = 1.16, 95% confidence interval = 1.05–1.27, p = 0.003 [Z test], I ² = 75.4%, p<0.001 [heterogeneity]).

Conclusions

The present meta-analysis confirmed the significant association of the rs9939609 variant in the FTO gene with CVD risk, which was independent of BMI and other conventional CVD risk factors.     

Association between Common Polymorphism near the MC4R Gene and Obesity Risk: A Systematic Review and Meta-Analysis

Background

Genome-wide association studies on Europeans have shown that two polymorphisms (rs17782313, rs12970134) near the melanocortin 4 receptor (MC4R) gene were associated with increased risk of obesity. Subsequently studies among different ethnic populations have shown mixed results with some confirming and others showing inconsistent results, especially among East Asians and Africans. We performed a comprehensive meta-analysis of various studies from different ethnic populations to assess the association of the MC4R polymorphism with obesity risk.

Methods

We retrieved all published literature that investigated association of MC4R variants with obesity from PubMed and Embase. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

A total of 61 studies (80,957 cases/220,223 controls) for rs17782313 polymorphism (or proxy) were included in the meta-analysis. The results suggested that rs17782313 polymorphism was significantly associated with obesity risk (OR = 1.18, 95%CI = 1.15–1.21, p<0.001). Similar trends were observed among subgroups of Europeans and East Asians, adults and children, studies with high quality score, and for each five MC4R polymorphisms independently.

Conclusions

The present meta-analysis confirms the significant association of MC4R polymorphism with risk of obesity. Further studies should be conducted to identify the causal variant and the underlying mechanisms of the identified association.     

The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis

MethodsWe conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1–19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study.ResultsThe pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3%) and 34.2% (95% CI: 27.8% to 41.2%) in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I² = 98%). There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT) was used to assess NAFLD compared with biopsies, ultrasound scan (USS) or magnetic resonance imaging (MRI).ConclusionsOur review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.     

Four Genetic Polymorphisms of Lymphotoxin-Alpha Gene and Cancer Risk: A Systematic Review and Meta-Analysis

Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the inflammatory and immunologic response. Numerous studies have shown LTA polymorphisms as risk factors for cancers, but the results remain inconclusive. The goal of the present meta-analyses is to establish the associations between cancers and four LTA variants (rs1041981, rs2239704, rs2229094 and rs746868). A total of 30 case-control studies involving 58,649 participants were included in the current meta-analyses. Our results showed significant associations with increased cancer risk for rs1041981 (odd ratio (OR) = 1.15, 99% confidential interval (CI) = 1.07-1.25, P < 0.0001, I² = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I² = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I² = 0.0%). No evidence was found for the association between rs746868 and cancer risk (OR = 1.01, 99% CI = 0.93-1.10, P = 0.771, I² = 0.0%). Subgroup meta-analysis suggested that rs2239704 was likely to increase the risk of hematological malignancy (OR = 1.10, 99% CI = 1.01–1.20, P = 0.023, I² = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I² = 0.0%). In conclusion, our meta-analyses suggested that the LTA rs1041981, rs2239704 and rs2229094 polymorphisms contributed to the increased risk of cancers. Future functional studies were needed to clarify the mechanistic roles of the three variants in the cancer risk.     

Pre-Pregnancy Body Mass Index in Relation to Infant Birth Weight and Offspring Overweight/Obesity: A Systematic Review and Meta-Analysis

Background

Overweight/obesity in women of childbearing age is a serious public-health problem. In China, the incidence of maternal overweight/obesity has been increasing. However, there is not a meta-analysis to determine if pre-pregnancy body mass index (BMI) is related to infant birth weight (BW) and offspring overweight/obesity.

Methods

Three electronic bibliographic databases (MEDLINE, EMBASE and CINAHL) were searched systematically from January 1970 to November 2012. The dichotomous data on pre-pregnancy overweight/obesity and BW or offspring overweight/obesity were extracted. Summary statistics (odds ratios, ORs) were used by Review Manager, version 5.1.7.

Results

After screening 665 citations from three electronic databases, we included 45 studies (most of high or medium quality). Compared with normal-weight mothers, pre-pregnancy underweight increased the risk of small for gestational age (SGA) (odds ratios [OR], 1.81; 95% confidence interval [CI], 1.76–1.87); low BW (OR, 1.47; 95% CI, 1.27–1.71). Pre-pregnancy overweight/obesity increased the risk of being large for gestational age (LGA) (OR, 1.53; 95% CI, 1.44–1.63; and OR, 2.08; 95% CI; 1.95–2.23), high BW (OR, 1.53; 95% CI, 1.44–1.63; and OR, 2.00; 95% CI; 1.84–2.18), macrosomia (OR, 1.67; 95% CI, 1.42–1.97; and OR, 3.23; 95% CI, 2.39–4.37), and subsequent offspring overweight/obesity (OR, 1.95; 95% CI, 1.77–2.13; and OR, 3.06; 95% CI, 2.68–3.49), respectively. Sensitivity analyses revealed that sample size, study method, quality grade of study, source of pre-pregnancy BMI or BW had a strong impact on the association between pre-pregnancy obesity and LGA. No significant evidence of publication bias was observed.

Conclusions

Pre-pregnancy underweight increases the risk of SGA and LBW; pre-pregnancy overweight/obesity increases the risk of LGA, HBW, macrosomia, and subsequent offspring overweight/obesity. A potential effect modification by maternal age, ethnicity, gestational weight gain, as well as the role of gestational diseases should be addressed in future studies.     

Self-Esteem and Obesity in Children and Adolescents: A Literature Review

The relationship between self-esteem and obesity has not received a great deal of empirical evaluation using strong research methodologies. Thus, it is not clear whether self-esteem is consistently related to obesity, whether the relationship is global or specific to physical appearance, whether the relationship differs by demographic variables such as age, gender or race/ethnicity, or whether self-esteem moderates weight changes during weight loss treatment programs. This review examines these questions using empirical evidence from 35 studies on the relationship between self-esteem and obesity in children and adolescents. Thirteen of 25 cross sectional studies clearly showed lower self-esteem in obese adolescents and children. Five of the six cross-sectional studies that included a measure of body esteem found lower body esteem in obese compared to normal weight children and adolescents. Results from two prospective studies examining initial self-esteem and later obesity were inconsistent. Results from six of eight treatment studies showed that weight loss treatment programs appear to improve self-esteem. However, it is unclear whether increases in self-esteem are related to enhanced weight loss. Many studies were methodologically weak primarily due to small and select samples and lack of appropriate comparison groups. Implications for prevention and treatment of childhood obesity are discussed.     

Birth Weight and Long-Term Overweight Risk: Systematic Review and a Meta-Analysis Including 643,902 Persons from 66 Studies and 26 Countries Globally

Background

Overweight is among the major challenging health risk factors. It has been claimed that birth weight, being a critical indicator of prenatal developmental conditions, is related to long-term overweight risk. In order to check this important assumption of developmental and preventive medicine, we performed a systematic review and comprehensive meta-analysis.

Methods and Findings

Relevant studies published up to January 2011 that investigated the relation between birth weight and later risk of overweight were identified through literature searches using MEDLINE and EMBASE. For meta-analysis, 66 studies from 26 countries and five continents were identified to be eligible, including 643,902 persons aged 1 to 75 years. We constructed random-effects and fixed-effects models, performed subgroup-analyses, influence-analyses, assessed heterogeneity and publication bias, performed meta-regression analysis as well as analysis of confounder adjusted data. Meta-regression revealed a linear positive relationship between birth weight and later overweight risk (p<0.001). Low birth weight (<2,500 g) was found to be followed by a decreased risk of overweight (odds ratio (OR) = 0.67; 95% confidence interval (CI) 0.59–0.76). High birth weight (>4,000 g) was associated with increased risk of overweight (OR = 1.66; 95% CI 1.55–1.77). Results did not change significantly by using normal birth weight (2,500–4,000 g) as reference category (OR = 0.73, 95% CI 0.63–0.84, and OR = 1.60, 95% CI 1.45–1.77, respectively). Subgroup- and influence-analyses revealed no indication for bias/confounding. Adjusted estimates indicate a doubling of long-term overweight risk in high as compared to normal birth weight subjects (OR = 1.96, 95% CI 1.43–2.67).

Conclusions

Findings demonstrate that low birth weight is followed by a decreased long-term risk of overweight, while high birth weight predisposes for later overweight. Preventing in-utero overnutrition, e.g., by avoiding maternal overnutrition, overweight and/or diabetes during pregnancy, might therefore be a promising strategy of genuine overweight prevention, globally.     

绿地与居民超重肥胖之间关系的Meta分析

已有研究表明,绿地与周边人群超重和肥胖风险存在潜在关联,然而其具体效应有待测定。采用Meta分析(meta-analysis)方法对69篇绿地与居民超重肥胖关系的研究结果进行统计分析,并探究了不同研究设计、绿地指标、样本年龄和不同尺度地理分析单元等亚组的研究结果差异,发现：(1)总体上,绿地与居民超重或肥胖风险、身体质量指数(body mass index, BMI)和腰围呈负相关关系,但不同研究设计类型(横截面研究和队列研究)之间的研究结果具有较大差异。(2)对于不同的绿地指标,其与居民超重肥胖的关系也存在一定差异。(3)相较于儿童和青少年,绿地与成年人超重肥胖的关联性更显著。(4)两者之间的关系具有明显的尺度效应。Meta分析结果显示,绿地与居民超重肥胖关系在各亚组中存在混杂,意味着它们的关系可能更加复杂,这对未来研究起到一定启示作用：应增加纵向研究以更深入探讨两者之间的因果关系和作用机理;构建完善的绿地测度指标体系,考虑多尺度地理分析单元的影响差异;同时,不应忽视来自样本多方面混杂因素的影响,从而使未来相关领域研究得出更明晰的结论,为城市绿地系统规划及相关政策制定提供科学依据。     

Gamma-Glutamyltransferase Level and Risk of Hypertension: A Systematic Review and Meta-Analysis

Background

Several prospective observational studies suggest that gamma-glutamyltransferase(GGT) level is positively associated with risk of hypertension. However, these studies draw inconsistent conclusions. Therefore, we conducted a systematic review and meta-analysis to evaluate the exact association between GGT level and subsequent development of hypertension.

Methods

We searched Pubmed, Embase, and Science Citation Index (ISI Web of Science) for prospective cohort studies examining the association between GGT level and hypertension. Then, pooled effect estimates (RRs) for the association between GGT level and hypertension were calculated.

Results

A total of 13 prospective cohort studies including 43314 participants and 5280 cases of hypertension were included. The pooled RR of hypertension was 1.94(95%CI: 1.55–2.43; P<0.001) when comparing the risk of hypertension between the highest versus lowest category of GGT levels. Moreover, the risk of hypertension increased by 23% (summary RR: 1.23; 95%CI: 1.13–1.32; P<0.001) per 1 SD logGGT increment. Subgroup analyses showed significant positive associations in each subgroup except in ≧160/95 subgroup (RR: 2.56, 95%CI: 0.87–7.54; P = 0.088) and nondrinkers subgroup (RR: 1.76, 95%CI: 0.88–3.53; P = 0.113). Sensitivity analyses showed no single study significantly affects the pooled RRs. No publication bias was found in our meta-analysis.

Conclusions

GGT level is positively associated with the development of hypertension. Further studies are needed to confirm our findings and elucidate the exact mechanisms between GGT level and the incidence of hypertension.     

Common Variant rs9939609 in Gene FTO Confers Risk to Polycystic Ovary Syndrome

Background

Fat mass and obesity-associated gene (FTO) has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size.

Method

This study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese.

Results

The less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09). Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06). To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups–obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28).

Conclusion

Variant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases.     

Metabolic Syndrome Risk after Gestational Diabetes: A Systematic Review and Meta-Analysis

Background

A number of studies have been conducted to investigate the risk of metabolic syndrome (MS) after gestational diabetes mellitus (GDM), but the results are contradictory. Accordingly, we performed a systematic review and meta-analysis to assess the association between these two conditions. The aim was to better understand the risks of MS with prior gestational diabetes.

Methods

Pubmed, ISI Web of Science, and Cochrane databases from September 1, 1979 to July 11, 2013 were searched to identify relevant studies. 17 studies containing 5832 women and 1149 MS events were included. We calculated the odds ratio (OR) with 95% confidence interval (CI) in analysis for each study using a random-effect or fixed-effect model. We also determined heterogeneity among these 17 articles and their publication bias.

Results

Women with a history of gestational diabetes had a significantly higher risk of MS than those who had a normal pregnancy (OR, 3.96; 95% CI, 2.99 to 5.26), but had significant heterogeneity (I ² = 52.6%). The effect remained robust (OR, 4.54; 95% CI, 3.78–5.46) in the subgroup of Caucasians, but no association (OR, 1.28; 95% CI, 0.64–2.56) was found in Asians. Heterogeneity was reduced (body mass index (BMI) matched group I ² = 14.2%, BMI higher in the GDM group I ² = 13.2%) in the subgroup of BMI. In addition, mothers with higher BMI in the GDM group had higher risk of MS than those in the BMI matched group (BMI higher in GDM group OR, 5.39; 95% CI, 4.47–6.50, BMI matched group OR, 2.53; 95% CI, 1.88–3.41).

Conclusions

This meta-analysis demonstrated increased risk of MS after gestational diabetes. Therefore, attention should be given to preventing or delaying the onset of MS in GDM mothers, particularly in Caucasian and obese mothers.     

Prevalence of Overweight among Inner City Hispanic‐American Children and Adolescents

Objective: National surveys have pointed to a particularly high risk of pediatric overweight among U.S. Hispanics. However, the data have been primarily from the Mexican‐American community. We studied the prevalence of overweight and clinical comorbidities in children and youth of predominantly El Salvadoran ancestry. Research Methods and Procedures: A sample of 309 Hispanic youth, 6–18 years was surveyed from two inner city Washington, DC, clinics. BMI; triceps skinfold (TSF) and subscapular skinfold thickness (SSSF); bioelectrical impedance analysis (BIA); and blood pressure measures were obtained, along with information regarding physical activity, sedentary behavior, dietary history, family, and personal medical history. Results: Thirty‐eight percent were overweight (BMI ≥ 95th percentile) and 22% at risk for overweight (BMI 85–94th percentile). Thirty‐four percent had TSF ≥ 90th percentile and 29% had SSSF ≥ 90th percentile. Fifty‐one percent of males and 70% of females had body fat > 30%. Compared to their nonoverweight counterparts, overweight youth had significantly higher systolic blood pressure (111.4 ± 1.3 vs. 104.5 ± 0.9 mm Hg, p < 0.0001). Among children younger than 11 years, overweight was associated with onset of adrenarche (23% vs. 10%, p = 0.01). Participation in one or more sports teams was negatively correlated with overweight) p = 0.04). Discussion: The prevalence of overweight and at risk for overweight in this sample was twice the national average for U.S. children and 1.7 times greater than that of Mexican‐American children in national surveys. Overweight was associated with advanced pubertal development, high body fat, elevated blood pressure, and decreased sports participation.     

Urban Environments and Obesity in Southeast Asia: A Systematic Review,Meta-Analysis and Meta-Regression

Many environmental factors contribute to the rise in prevalence of obesity in populations but one key driver is urbanization. Countries in Southeast (SE) Asia have undergone rapid changes in urbanization in recent decades. The aim of this study is to provide a systematic review of studies exploring the relationship between living in an urban or rural environment (urbanicity) and obesity in Southeast Asia. In particular, the review will investigate whether the associations are uniform across countries and ages, and by sex. The literature search was conducted up to June 2014 using five databases: EMBASE, PubMed, GlobalHealth, DigitalJournal and Open Grey. Forty-five articles representing eight of the eleven countries in SE Asia were included in the review. The review found a consistent positive association between urbanicity and obesity in countries of Southeast Asia, in all age groups and both genders. Regional differences between the associations are partly explained by gross national income (GNI). In countries with lower GNI per capita, the association between urbanicity and obesity was greater. Such findings have implications for policy makers. They imply that population level interventions need to be country or region specific, tailored to suit the current stage of economic development. In addition, less developed countries might be more vulnerable to the negative health impact of urbanization than more developed countries.     

The Effect of Exercise on Visceral Adipose Tissue in Overweight Adults: A Systematic Review and Meta-Analysis

Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects) fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with “The Critical Review Form for Quantitative Studies”. Using random-effects weights, the standardized mean difference (Hedge''s g) of the change in visceral adipose tissue was −0.497 with a 95% confidence interval of −0.655 to −0.340. The Z-value was −6.183 and the p-value (two tailed) was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm² (on CT analysis) in women and more than 40 cm² in men, even after 12 weeks.     

Insulin Therapy and Risk of Prostate Cancer: a Systematic Review and Meta-Analysis of Observational Studies

Background

Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM).

Method

A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed.

Result

A total of 11 (10 cohorts, and one case–control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly.

Conclusions

Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions.