Person:

Song, Yiqing

Objective: Both in vitro and in vivo studies indicate that metformin inhibits cancer cell growth and reduces cancer risk. Recent epidemiological studies suggest that metformin therapy may reduce the risks of cancer and overall cancer mortality among patients with type 2 diabetes. However, data on its effect on colorectal cancer are limited and inconsistent. We therefore pooled data currently available to examine the association between metformin therapy and colorectal cancer among patients with type 2 diabetes. Research Design and Methods: The PubMed and SciVerse Scopus databases were searched to identify studies that examined the effect of metformin therapy on colorectal cancer among patients with type 2 diabetes. Summary effect estimates were derived using a random-effects meta-analysis model. Results: The analysis included five studies comprising 108,161 patients with type 2 diabetes. Metformin treatment was associated with a significantly lower risk of colorectal neoplasm (relative risk [RR] 0.63 [95% CI 0.50–0.79]; P < 0.001). After exclusion of one study that investigated colorectal adenoma, the remaining four studies comprised 107,961 diabetic patients and 589 incident colorectal cancer cases during follow-up. Metformin treatment was associated with a significantly lower risk of colorectal cancer (0.63 [0.47–0.84]; P = 0.002). There was no evidence for the presence of significant heterogeneity between the five studies (Q = 4.86, P = 0.30; I2 = 18%). Conclusions: From observational studies, metformin therapy appears to be associated with a significantly lower risk of colorectal cancer in patients with type 2 diabetes. Further investigation is warranted.

Background: Ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7) play a central role in magnesium homeostasis, which is critical for maintaining glucose and insulin metabolism. However, it is unclear whether common genetic variation in TRPM6 and TRPM7 contributes to risk of type 2 diabetes. Methods: We conducted a nested case-control study in the Women's Health Study. During a median of 10 years of follow-up, 359 incident diabetes cases were diagnosed and matched by age and ethnicity with 359 controls. We analyzed 20 haplotype-tagging single nucleotide polymorphisms (SNPs) in TRPM6 and 5 common SNPs in TRPM7 for their association with diabetes risk. Results: Overall, there was no robust and significant association between any single SNP and diabetes risk. Neither was there any evidence of association between common TRPM6 and TRPM7 haplotypes and diabetes risk. Our haplotype analyses suggested a significant risk of type 2 diabetes among carriers of both the rare alleles from two non-synomous SNPs in TRPM6 (Val1393Ile in exon 26 [rs3750425] and Lys1584Glu in exon 27 [rs2274924]) when their magnesium intake was lower than 250 mg per day. Compared with non-carriers, women who were carriers of the haplotype 1393Ile-1584Glu had an increased risk of type 2 diabetes (OR, 4.92, 95% CI, 1.05–23.0) only when they had low magnesium intake (less than 250 mg/day). Conclusion: Our results provide suggestive evidence that two common non-synonymous TRPM6 coding region variants, Ile1393Val and Lys1584Glu polymorphisms, might confer susceptibility to type 2 diabetes in women with low magnesium intake. Further replication in large-scale studies is warranted.

OBJECTIVE—To examine whether day napping or short night sleeping is associated with higher risk of diabetes. RESEARCH DESIGN AND METHODS—This was a prospective study of hours of day napping and night sleeping assessed in 1996–1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants in the National Institutes of Health (NIH)-AARP Diet and Health Study. Odds ratios (ORs) and 95% CI were derived from multivariate logistic regression models. RESULTS—Longer day napping was associated with a higher risk of diabetes. After adjustment for potential confounders, ORs were 1.23 (95% CI 1.18–1.29) for those reporting <1 h and 1.55 (95% CI 1.45–1.66) for those reporting ≥1 h of napping compared with individuals who did not nap ((P_{trend}) < 0.0001). For night sleeping, with 7–8 h as the referent, the OR was 1.46 (95% CI 1.31–1.63) for <5 h, 1.11 (1.06–1.16) for 5–6 h, and 1.11 (0.99–1.24) for ≥9 h. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes ((P_{interaction}) < 0.0001). Among participants with no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with ≥1 h of napping, both long and short sleeping was associated with higher risk. CONCLUSIONS—Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit.

Background: Type 2 diabetes is becoming an epidemic in China. To evaluate the prevalence, clustering of metabolic risk factors and their impact on type 2 diabetes, we conducted a population-based study in Shanghai, China's largest metropolitan area. Methods: From 2006 to 2007, 2,113 type 2 diabetes cases and 2,458 comparable controls of adults aged 40 to 79 years were enrolled. Demographic, lifestyle, and dietary factors were assessed via standardized questionnaires. Plasma, red and white blood cells were collected and stored for future studies. Anthropometric indices and biochemical intermediates (including blood pressure, fasting glucose, glycosylated hemoglobin, and blood lipids) were measured. The prevalence of metabolic syndrome were also compared following two criteria recommended by the Chinese Diabetes Society (CDS, 2004) and the National Cholesterol Education Program's Adult Treatment Panel III (ATP III, 2002). Results: Prevalence of metabolic syndrome (62% vs. 15% using CDS criteria) and its individual components, including obesity (51% vs. 42%), hypertension (54% vs. 41%), hypertriglyceridemia (42% vs. 32%), and low high-density lipoprotein-cholesterol (HDL) levels (36% vs. 25%) were higher in diabetes cases than controls. Regardless of criteria used, those with impaired fasting glucose (IFG) had similarly high prevalence of metabolic syndrome as did diabetes cases. In a multiple logistic regression model adjusted for demographics and lifestyle risk factors, the odds ratios of diabetes (95% CI) were 1.23 (1.04-1.45) for overweight (28 >= BMI >= 24), 1.81 (1.45-2.25) for obesity (BMI > 28), 1.53 (1.30-1.80) for central obesity (waist circumference > 80 cm for woman or waist circumference > 85 cm for man), 1.36 (1.17-1.59) for hypertension (sbp/dbp >= 140/90 mmHg), 1.55 (1.32-1.82) for high triglycerides (triglycerides > 1.70 mmol/l) and 1.52 (1.23-1.79) for low HDL-C (HDL-C < 1.04 mmol/L). Conclusions: These data indicate that multiple metabolic risk factors--individually or jointly--were more prevalent in diabetes patients than in controls. Further research will examine hypotheses concerning the high prevalence of IFG, family history, and central obesity, aiding development of multifaceted preventive strategies specific to this population.

Objective: To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes. Research Design and Methods: A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50–<75, (\geq)75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors. Results: Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial. Conclusions: Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.

Aims/hypothesis: (FTO) harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for (FTO) in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the (FTO) locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods: All studies published on the association between (FTO)-rs9939609 (or proxy [r(^2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results: The (FTO)-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(^{−19})), overweight by 1.13-fold/allele (p = 1.0 × 10(^{−11})) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(^{−8})). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(^{−5})). The (FTO)-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10(^{−17})), WHR by 0.003/allele (p = 1.2 × 10(^{−6})), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of (FTO) variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation: (FTO) is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, (FTO) is also associated with type 2 diabetes independently of BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

OBJECTIVE: Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged ≥40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group. RESULTS: During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79–1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76–1.10]; P = 0.36). CONCLUSIONS: Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.

OBJECTIVE: Understanding the relationship between multivitamin use and diabetes risk is important given the wide use of multivitamin supplements among U.S. adults. RESEARCH DESIGN AND METHODS: We prospectively examined supplemental use of multivitamins and individual vitamins and minerals assessed in 1995–1996 in relation to self-reported diabetes diagnosed after 2000 among 232,007 participants in the National Institutes of Health–American Association of Retired Persons Diet and Health Study. Multivitamin use was assessed by a food-frequency questionnaire at baseline. Odds ratios (ORs) and 95% CIs were calculated by logistic regression models, adjusted for potential confounders. In total, 14,130 cases of diabetes diagnosed after 2000 were included in the analysis. RESULTS: Frequent use of any multivitamins was not associated with risk of diabetes after adjustment for potential confounders and uses of individual supplements. Compared with nonusers of any multivitamins, the multivariate ORs among users were 1.07 (95% CI 0.94–1.21) for taking vitamins less than once per week, 0.97 (0.88–1.06) for one to three times per week, 0.92 (0.84–1.00) for four to six times per week, and 1.02 (0.98–1.06) for seven or more times per week (P for trend = 0.64). Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements. The multivariate ORs comparing daily users with nonusers were 0.91 (0.86–0.97) for vitamin C supplements and 0.85 (0.80–0.90) for calcium supplements. Use of vitamin E or other individual vitamin and mineral supplements were not associated with diabetes risk. CONCLUSIONS: In this large cohort of U.S. older adults, multivitamin use was not associated with diabetes risk. The findings of lower diabetes risk among frequent users of vitamin C or calcium supplements warrant further evaluations.

OBJECTIVE: Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone–binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw. RESULTS: Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23–0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31–1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG. CONCLUSIONS: Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women.

Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women’s Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90–1.11) in whites, 0.95 (0.85–1.06) in blacks, 0.96 (0.79–1.17) in Hispanics, and 0.88 (0.70–1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.