High-fibre, low-fat diet predicts long-term weight loss and decreased type 2 diabetes risk: the Finnish Diabetes Prevention Study

Aims/hypothesis The aim of this study was to investigate the association of dietary macronutrient composition and energy density with the change in body weight and waist circumference and diabetes incidence in the Finnish Diabetes Prevention Study.Subjects and methods Overweight, middle-aged men (n=172) and women (n=350) with impaired glucose tolerance were randomised to receive either ‘standard care’ (control) or intensive dietary and exercise counselling. Baseline and annual examinations included assessment of dietary intake with 3-day food records and diabetes status by repeated 75-g OGTTs. For these analyses the treatment groups were combined and only subjects with follow-up data (n=500) were included.Results Individuals with low fat (<median) and high fibre (>median) intakes lost more weight compared with those consuming a high-fat (>median), low-fibre (<median) diet (3.1 vs 0.7 kg after 3 years). In separate models, hazard ratios for diabetes incidence during a mean follow-up of 4.1 years were (highest compared with lowest quartile) 0.38 (95% CI 0.19–0.77) for fibre intake, 2.14 (95% CI 1.16–3.92) for fat intake, and 1.73 (95% CI 0.89–3.38) for saturated-fat intake, after adjustment for sex, intervention assignment, weight and weight change, physical activity, baseline 2-h plasma glucose and intake of the nutrient being investigated. Compared with the low-fat/high-fibre category, hazard ratios were 1.98 (95% CI 0.98–4.02), 2.68 (95% CI 1.40–5.10), and 1.89 (95% CI 1.09–3.30) for low-fat/low-fibre, high-fat/high-fibre, and high-fat/low-fibre, respectively.Conclusions/interpretation Dietary fat and fibre intake are significant predictors of sustained weight reduction and progression to type 2 diabetes in high-risk subjects, even after adjustment for other risk factors.     

瘦素受体第20外显子基因变异与2型糖尿病的关系探讨

瘦素是肥胖基因编码的一种脂源性激素 ,它与位于下丘脑和脂肪组织的瘦素受体结合后 ,发挥调节能量代谢和体脂平衡的作用。瘦素受体基因 ,又被称为糖尿病基因〔1〕,于1995年被定位克隆〔2〕,目前已在其 2 0个外显子中发现 19种基因多态性 ,但关于该基因变异与肥胖和糖尿病的关系 ,众家报道不一〔3 ,4〕。本实验选择其胞内区第 2 0外显子 ,检测其 2 92 7位核苷酸Ｃ→Ａ变异和 30 5 7位核苷酸Ｇ→Ａ变异频率〔4〕,并探讨其变异与 2型糖尿病的关系。一、对象和方法1.研究对象 :选取湖北地区的 2型糖尿病住院患者 10 6例 (按 1997年ＡＤＡ的诊断…     

胰升糖素受体基因变异与2型糖尿病的关系

目的探讨中国人２型糖尿病与胰升糖素受体（ＧＣＧＲ）基因４０号密码子的错义突变（Ｇｌｙ４０Ｓｅｒ）是否存在关联。方法运用聚合酶链反应—限制性片段长度多态性（ＰＣＲＲＦＬＰ）分析方法在２００例无亲缘关系之中国云南昆明地区汉族人（２型糖尿病患者１２０例,健康对照者８０例）中对ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变进行检测。结果本文所有研究对象中无论是２型糖尿病患者还是健康对照者均无一例存在ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变,其ＧＣＧＲ基因４０号密码子的基因型均表现为Ｇｌｙ４０／Ｇｌｙ４０之纯合子,Ｇｌｙ４０和Ｓｅｒ４０等位基因频率均分别为１和０。２型糖尿病患者与健康对照者无任何差异。结论在中国云南昆明地区的汉族人中,ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变与２型糖尿病不存在任何关联     

瘦素受体基因变异与2型糖尿病各临床变量的关系

目的 研究瘦素受体基因（leptin receptor,Lepr)第20外显子基因变异与2型糖尿病患者各临床变量（如体重指数、腰围、臀围、收缩压、舒张压、空腹血糖、甘油三酯、总胆固醇等）的关系。方法 用聚合酶链反应－限制性酶切片段长度多态性（PCR－RFLP）测定90例2型糖尿病患者Lper第20外显子基因变异频率，常规检测血糖、甘油三酯、总胆固醇和高密度脂蛋白，于相同条件下测身高、体重，腰围和臀围，按公式计算体重指数（BMI）、脂肪百分比（％Fat)和胰岛素敏感指数（ISI）。结果 中国湖北地区糖尿病患者中存在Lepr第20外显子基因变异，其中2927位C→A（Ala976Asp)变异频率为100％，3057位G→A（Pro1019Pro)总的变异频率为80％；其3057位G→A变异与肥胖型2型糖尿病患者的胰岛素敏感指数呈负相关（P＜0.001)，与女性糖尿病患者的腰围／臀围呈正相关（P＜0.05)；Logistic回归分析发现，Lepr基因3057位G→A变异与体重指数（BMI）、腰围／臀围、舒张压、甘油三酯呈正相关，与高密度脂蛋白及ISI呈负相关。结论 中国人糖尿病患者中存在Lepr第20外显子基因变异，其变异主要影响2型糖尿病患者脂质代谢、局部体脂分布并参与胰岛素抵抗的发生。     

Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations

BACKGROUND: Leptin is an adipocyte secreted hormone involved in regulation of body weight and metabolism in man. Placenta leptin levels correlate positively with birth weight. It is therefore possible that variation in the leptin receptor gene (LEPR) may contribute to obesity and influence birth weight. OBJECTIVE: This study investigates the influence of the leptin receptor gene variant Gln223Arg (A-->G, 668), on maternal body mass index (BMI), foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian (India, Bangladesh, Pakistan) and UK/Irish origin. RESULTS: Maternal genotype distributions did not differ from those expected under Hardy-Weinberg equilibrium conditions in either population of origin. Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no significant association with foetal birth weight (adjusted for gestational length) or with maternal BMI during first trimester (adjusted for age) in either population group. CONCLUSION: These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight, and is not associated with variation in maternal BMI in early pregnancy in our sample.     

脂肪分化相关蛋白基因与2型糖尿病相关

目的通过单核苷酸多态性(SNP)的检测及基因分型来研究脂肪分化相关蛋白基因(ADRP)与2型糖尿病的相关性。方法使用PCR测序方法,对ADRP基因的启动子、外显子以及临近的内含子,分别在正常人群、2型糖尿病人群进行测序,确定该基因是否与华东地区汉族2型糖尿病患者相关。结果所测ADRP基因片段总长度5003个碱基,有23个SNP,高频、低频分别是5个、18个。启动子的一个SNP(P/-407)在2型糖尿病人群与正常人群的等位基因型、基因型差异均有显著性(P<0.05);两个错义突变Ser251Pro、Thr396Ala分别在两个2型糖尿病家系中传递。结论ADRP可能与华东地区汉族人2型糖尿病相关。     

The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability

Genetic variation at the leptin receptor gene locus may play an important role in the pathophysiology of human obesity, a leptin-resistant state. Previous studies exploring potential associations between leptin receptor gene polymorphisms and obesity have reported conflicting results. The aim of this study was to evaluate a genetically homogeneous population for associations between body composition variables and three common leptin receptor gene polymorphisms (K109R, Q223R, and K656N) that have potential functional significance as well as to assess the contributions of these polymorphisms to the variability of obesity. One hundred and eighteen consecutively enrolled subjects (62 women: mean age, 17.5 +/- 1.6 yr; body mass index range, 16.2-30.1; 56 men: mean age, 17.8 +/- 1.8 yr; body mass index range, 15.4-35.9) were genotyped for the three polymorphisms, and their body mass index, sum of 4 skinfolds, fat-free mass, percent fat mass, serum leptin levels, caloric intake, fat intake, and exercise patterns were determined. Allele frequencies were estimated by the gene-counting method, and genotype distributions between 89 normal weight (body mass index, < or =25 kg/m(2)) and 29 overweight-obese (body mass index, >25 kg/m(2)) subjects were compared using chi(2) test (using codominant, dominant, and recessive models). Analysis of covariance was also performed to evaluate associations between the polymorphisms and body composition variables after controlling for potential confounders. For the Q223R polymorphism, there was a higher prevalence of the R223 allele in the homozygous form among overweight-obese subjects vs. normal weight subjects (20.7% vs. 4.5%; P = 0.01). Furthermore, simple and multiple regression analyses revealed that the R223 allele in the homozygous form is a significant predictor of both body mass index (P = 0.015) and percent fat mass (P = 0.02) even after adjusting for age and gender and explains 4.5% of the variance in percent fat mass and 5% of the variance in body mass index. There was no significant difference in allele frequencies or genotype distributions for the K109R or K656N polymorphisms. These findings support the hypothesis that the Q223R polymorphism (but not the K109R or K656N polymorphism) of the leptin receptor gene is associated with obesity and predicts a small percentage of body weight and body composition variability in a genetically homogeneous population.     

Gene-diet interaction in relation to the prevention of obesity and type 2 diabetes: evidence from the Finnish Diabetes Prevention Study

Both genetic and environmental factors are involved in the pathogenesis of obesity and type 2 diabetes. Most of the genetic studies on common obesity are confined to the links between a given gene polymorphism or gene loci and different phenotypes of obesity or anthropometric measures. Some studies indicate that genetic factors modify the weight reduction response to energy restriction or weight gain in the long-term. Only a few studies have focused on gene-diet interaction in the development of type 2 diabetes. The Finnish Diabetes Prevention Study shows (DPS) that the success of a lifestyle intervention depends also on the polymorphisms of those genes, which are suggested to play a role in energy metabolism, lipid metabolism, insulin resistance or insulin secretion. This review deals with selected genes examined so far in the DPS.     

Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women

OBJECTIVE: Bone mineral density (BMD) is under strong genetic control and a number of candidate genes have been associated with BMD. Both muscle strength and body weight are considered to be important predictors of BMD but far less is known about the genes affecting muscle strength and fat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmI SNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthy women. DESIGN: A population-based study of 175 healthy women aged 20-39 years was used. METHODS: The polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) were amplified by PCR. Body mass measurements (fat mass, lean mass, body weight and body mass index) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. RESULTS: Individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site (BB) have higher hamstring strength (ss vs LL, P=0.02), body weight (ss vs LL, P=0.049) and fat mass (ss vs LL, P=0.04) compared with women with a longer poly A repeat (LL) and/or the presence of the linked BsmI restriction site (bb). CONCLUSIONS: Genetic variation in the VDR is correlated with muscle strength, fat mass and body weight in premenopausal women. Further functional studies on the poly A microsatellite are needed to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkage disequilibrium with a functional variant in a closely situated gene further downstream of the VDR 3'UTR.     

Beta(2)-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes

The aim of this study was to investigate whether polymorphisms in the beta(2)-adrenergic receptor gene (5'LC-Arg19Cys, Arg16Gly, Gln27Glu) are associated with hypertension in patients with or without type 2 diabetes and with the blood pressure levels in normotensive sib pairs. The association study included 291 hypertensive patients without type 2 diabetes, 124 hypertensive patients with type 2 diabetes, and 265 healthy control subjects from SWEDEN: In addition, normotensive sib pairs that were discordant for the Arg16Gly (72 pairs) and Gln27Glu (40 pairs) polymorphisms were identified in type 2 diabetes families from FINLAND: Genotyping was performed using polymerase chain reaction-restriction fragment-length polymorphism analysis. Homozygous carriers of the Arg16 allele had a significantly increased odds ratio (OR) for hypertension in patients with type 2 diabetes (OR 2.14; 95% confidence interval [CI], 1.05 to 4.33), particularly among lean (body mass index<27 kg/m(2)) patients (OR 3.47; 95% CI, 1.06 to 11.33). The Gln27 allele showed a weaker association to hypertension (OR 1.55; 95% CI, 1.00 to 2.41) and was found to be in linkage disequilibrium with the Cys19 allele of the 5'LC-Arg19Cys polymorphism. In the paired-sibling analysis, siblings with at least 1 copy of the Arg16 allele had higher systolic blood pressure (P=0.049), and nondiabetic siblings had a higher body mass index (P=0.026) than siblings homozygous for the Gly16 allele. These results indicate that the Arg16 allele of the beta(2)-adrenergic receptor gene confers an increased risk for hypertension in subjects with type 2 diabetes and is associated with higher blood pressure levels and higher body mass index in sib pairs who are discordant for the polymorphism.     

Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study

Aims/hypothesis Adiponectin is a circulating peptide derived from adipose tissue. It mediates its insulin-sensitising and anti-atherogenic effects on target tissues through two known receptors, adiponectin receptors 1 and 2 (ADIPOR1; ADIPOR2), which are encoded by the genes ADIPOR1 and ADIPOR2. Our aim was to study the association of ADIPOR1 gene variations with body size and risk of type 2 diabetes in subjects with impaired glucose tolerance, who participated in the Finnish Diabetes Prevention Study (DPS).Subjects and methods We selected seven single nucleotide polymorphisms (SNPs) of the ADIPOR1 gene to perform association studies with anthropometrics and metabolic parameters at baseline, and with the risk of type 2 diabetes during the 3-year follow-up in the DPS study population. Both single SNP analysis and haplotype effects were studied.Results Three out of seven markers studied (rs10920534, rs22757538 and rs1342387) were significantly associated with various body size measurements including weight, height, waist and hip circumference, sagittal diameter and body mass index. Furthermore, three markers (rs10920534, rs12045862 and rs7539542), of which two were different from those associating with body size, were linked to fasting and 2-h insulin levels, particularly in men at baseline. The haplotype analysis with five markers revealed seven major haplotypes in the DPS study population. The haplotype effects on body size measures were in line with those of single SNP analysis. However, none of the markers were associated with the risk of type 2 diabetes.Conclusions/interpretation Our findings suggest that ADIPOR1 has a putative role in the development of body size, and that traits for central adiposity and insulin resistance may be dissociated from each other.Electronic Supplementary Material Supplementary Material is available in the online version of this article at     

The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus

OBJECTIVE: A single nucleotide polymorphism (A1220G; N363S) in exon 2 of the glucocorticoid receptor gene (NR3C1), associated with increased sensitivity to glucocorticoids, was shown to be associated with obesity in nondiabetic subjects. Here, we investigated the impact of this variant on traits related to obesity and hyperglycaemia in subjects with type 2 diabetes mellitus. PATIENTS AND MEASUREMENTS: The N363S variant was screened by restriction fragment length polymorphism technique following DNA amplification by polymerase chain reaction in 369 French Caucasians with type 2 diabetes mellitus. RESULTS: Twenty subjects were found to be heterozygous for the variant (AG genotype frequency 0.0542). The prevalence of overweight [body mass index (BMI) > 25 kg/m2] was higher in AG carriers than in AA carriers (100%vs. 73%, P = 0.003). Moreover, the mean body weight and the BMI were higher in AG as compared to AA carriers, although only the body weight was significantly different between groups. However, when only the men were considered, a significantly higher BMI was observed in AG as compared to AA carriers: 30.0 +/- 4.8 vs. 27.3 +/- 4.6 kg/m2 (BMI Z-score 1.28 +/- 1.38 vs. 0.55 +/- 1.17; P = 0.035). No evidence was found for an association of the N363S variant with parameters related to the severity of hyperglycaemia. CONCLUSIONS: The 363S allele of the N363S variant of NR3C1 is associated with the susceptibility to overweight in subjects with type 2 diabetes mellitus.     

Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China

Background and Aim:  To investigate the relationship between human leptin receptor ( LEPR ) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non-alcoholic fatty liver disease (NAFLD).
Methods:  Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were recruited. Hemi-nested polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic parameters were measured routinely. Liver ultrasound was carried out for all subjects.
Results:  T2DM patients complicated with NAFLD had higher plasma insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels than those without NAFLD and NGT subjects. The variant frequency at nucleotide 3057 G→A transversion was 76.0% in type 2 diabetic patients complicated with NAFLD, which was also significantly higher than those without NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in genotype distribution between the three groups (χ² = 14.63, P  < 0.01).
Conclusion:  The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD by regulating lipid metabolism and affecting insulin sensitivity.     

瘦素受体基因Gln223Arg变异与浙南地区2型糖尿病的相关性研究

目的 研究瘦素受体Gln223Arg基因多态性与2型糖尿病(T2DM)的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定无亲缘关系的336例浙南地区汉人的瘦素受体基因Gln223Arg的基因型(其中T2DM合并肥胖组121例,T2DM非肥胖组104例,正常对照组111例),并分析Gln223Arg基因多态性与糖尿病的关系.结果 ① T2DM肥胖组Gln223Arg基因型GG、GA及AA的频率分别为0.645、0.347和0.008;G和A等位基因频率分别为0.818和0.182;T2DM非肥胖组基因型GG和GA的频率分别为0.769、0.231;G和A等位基因频率分别为0.885和0.115;正常对照组基因型GG、GA及AA的频率分别为0.802、0.189和0.009;G和A等位基因频率分别为0.896和0.104.②T2DM合并肥胖组A、G等位基因分布频率与正常对照组比较差异有显著性(P＜0.05),非肥胖组与正常对照组比较无明显差异(P＞0.05).结论 浙南地区汉族人群存在瘦素受体基因Gln223Arg变异,它可能是该地区人群T2DM合并肥胖患者的遗传易感标记,A等位基因与T2DM发病有一定关系.