Protocol: Alcohol consumption and diabetes risk factors: a meta-analysis of interventional studies

Transcription

1 Protocol: Alcohol consumption and diabetes risk factors: a meta-analysis of interventional studies Version: 1 Date: Study team: C Mary Schooling, CUNY School of Public Health at Hunter College, 2180 Third Avenue, New York, NY 10035, USA Chen Shen, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, CHINA. Lin Xu, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, CHINA. Jie Zhao, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, CHINA.

2 Introduction With the economic development, type 2 diabetes is becoming one of the most common chronic diseases around the world. 1, 2 Genetic and lifestyle factors such as physical inactivity and obesity play important roles in the development of diabetes. 3 Alcohol is also prevalent in daily life. Longitudinal observational studies, mainly from developed Western settings, have shown that moderate alcohol consumption is associated with lower risk of diabetes. 4, 5 Plausible biological reasons exist for these associations, for example alcohol is a well-known risk factor for breast cancer, 6, 7 most likely through raising estrogens, in men and women. Alcohol is also thought to reduce testosterone, 8 although the experimental evidence is limited. Randomized controlled trials have shown that estrogen protects against diabetes, 9 while testosterone improves glucose metabolism. 10 Thus alcohol use might be expected to protect against diabetes in women, but not men. On the other hand, observational studies are vulnerable to several limitations including residual confounding, reverse causality due to incomplete understanding of the biological mechanism. Moderate alcohol users from commonly studied Western settings are increasingly heavily self-selected healthy users, with healthier 11, 12 lifestyle behaviors, higher socioeconomic position and better health status, making findings from these studies open to residual confounding. Previous systematic reviews have only reported the outcomes of observational studies Interventions where alcohol is experimentally manipulated are much less vulnerable to confounding, and may help determine the biological effects of alcohol in the development of diabetes, which has important policy implications. In this meta-analysis, we will use interventional studies to systematically assess the effect of alcohol consumption on biological markers associated with the development of type 2 diabetes including glycemia, insulin and glycosylated hemoglobin. Review question What is the effect of alcohol use on risk factors of diabetes? Eligibility criteria Studies will be eligible if they meet all the following criteria Studies using alcohol as intervention including randomized controlled trials, before and after studies or crossover studies. Duration of the intervention studies more than one week, because this study concerns the effect of regular alcohol consumption on glucose metabolism, rather than the acute effect.

3 Published or registered intervention studies where we are able to obtain the results Any date, because there is no reason to think that the effect of alcohol consumption on type 2 diabetes has changed over time Any setting, because there is no reason to think that the effect of alcohol consumption on type 2 diabetes varies by ethnicity Reported in English, because a preliminary search of the literature suggests all studies are in English The relevant outcomes will be biological markers related to glucose metabolism. These include plasma glucose, serum insulin and glycosylated hemoglobin. Information Sources We will search PubMed, Embase and the Cochrane Library database for intervention studies reporting alcohol consumption and relevant biomarkers of glucose metabolism. Where we find duplicate publications from the same study we will include the report that includes an assessment of changes in glucose metabolism related biomarkers by arm at intervention completion. We will search from the beginning of time until the end of December If there is a significant delay between completion and publication, we will update the search to the current date. We will also search all published reviews on this topic to identify any additional studies. Finally, we will search the references of any included studies to check that our search has been comprehensive. Search We will search PubMed using alcohol AND (trial OR before ADJ after OR crossover) AND (diabetes OR insulin OR glucose OR hba) in title, abstract or any field with the selection limited to English. The search strategy for Embase and Cochrane library will be similar. To check our search, we will also search the WHO trials database for any studies with alcohol as the intervention. We will also search the references of any included study. Both published and unpublished studies will be eligible for inclusion. Study selection Two people will search independently and compare their selections at the end of the search process. Any differences will be resolved by consensus or if necessary by reference to a third investigator. We will not exclude the studies based on the number of participants, because we

4 want to make full use of the available evidence. We will exclude the studies which assess the acute effect of alcohol consumption on glucose metabolism. Selection process After the primary search for these databases, we will screen the titles and abstracts. Then we will screen the remaining publications on the basis of the corresponding full text for evaluation of the level of plasma glucose, serum insulin and glycosylated hemoglobin. Data extraction A statistician will abstract data from the selected studies using a standard template. Data items We will extract the following information for each study Publication details (author, year of publication, title, journal and funding) Study design (before and after, crossover, random crossover, randomized two arm) and information about implementation Characteristics of participants, including health status, pre-intervention drinking status, age, sex and setting Duration of follow-up Dose of alcohol consumption and method of administration Primary study outcome Number of participants in each arm at start and end (alcohol and control groups) Biomarkers assessment Bias assessment for individual studies We will use an established tool (Jadad scale) to evaluate the quality of each study. 17 Two investigators will independently rate each study and settle any differences by consensus or reference to a third investigator. Summary Measure The principal summary measure will be a measure of mean difference. Synthesis of results Heterogeneity will be analyzed by using the Cochran Q test (chi square) and I 2

5 statistics. I 2 is the proportion of total variation observed between the studies attributable to differences between studies rather than to sampling error (chance), with the values less than 30% representing low variation, less than 60% moderate variation, and greater than 60% high variation. Whether to use a fixed or random effects model to pool studies will be determined by using this criterion. We will use R to do the analysis. Bias Assessment for all studies We will use Begg and Egger s methods to assess publication bias. Funnel plot will also be used to identify publication bias and trim and fill will be used to correct for publication bias, if any. Subgroup analysis The effects of alcohol consumption on glucose metabolism may differ by sex. We will use meta-regression to assess whether the effects of alcohol on glucose metabolism vary with sex. We will also do sub-group analysis by study design and quality. Statistical analysis We will use mean difference as the summary statistic.

6 References 1. Hu FB. Globalization of Diabetes The role of diet, lifestyle, and genes. Diabetes care. 2011; 34: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for Diabetes care. 2004; 27: Bruno G, Landi A. Epidemiology and costs of diabetes. Transplantation proceedings. 2011; 43: Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes care. 2005; 28: Stampfer MJ, Colditz GA, Willett WC, Manson JE, Arky RA, Hennekens CH, et al. A prospective study of moderate alcohol drinking and risk of diabetes in women. Am J Epidemiol. 1988; 128: Singletary KW, Gapstur SM. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. Jama. 2001; 286: Chen WY, Rosner B, Hankinson SE, Colditz GA, Willett WC. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. Jama. 2011; 306: Sierksma A, Sarkola T, Eriksson CJ, van der Gaag MS, Grobbee DE, Hendriks HF. Effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate, testosterone, and estradiol levels in middle-aged men and postmenopausal women: a diet-controlled intervention study. Alcoholism, clinical and experimental research. 2004; 28: Bonds DE, Lasser N, Qi L, Brzyski R, Caan B, Heiss G, et al. The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial. Diabetologia. 2006; 49: Cai X, Tian Y, Wu T, Cao CX, Li H, Wang KJ. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian journal of andrology. 2014; 16: Fillmore KM, Golding JM, Graves KL, Kniep S, Leino EV, Romelsjo A, et al. Alcohol consumption and mortality. I. Characteristics of drinking groups. Addiction. 1998; 93: Fillmore KM, Kerr WC, Stockwell T, Chikritzhs T, Bostrom A. Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies. Addiction Research & Theory. 2006; 14: Carlsson S, Hammar N, Grill V. Alcohol consumption and type 2 diabetes

7 Meta-analysis of epidemiological studies indicates a U-shaped relationship. Diabetologia. 2005; 48: Conigrave KM, Rimm EB. Alcohol for the prevention of type 2 diabetes mellitus? Treatments in endocrinology. 2003; 2: Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med. 2004; 140: Pietraszek A, Gregersen S, Hermansen K. Alcohol and type 2 diabetes. A review. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2010; 20: Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled clinical trials. 1996; 17:1-12.