Benefits of bariatric surgery on microvascular outcomes in adult patients with type 2 diabetes: a systematic review and meta-analysis

BackgroundMicrovascular diabetes complications impair patients’ health-related quality of life. Bariatric surgery (BS) emerged as a compelling treatment that demonstrated to have beneficial effects on patients with diabetes and obesity.ObjectiveWe aimed to synthesize the benefit of bariatric surgery on microvascular outcomes in adult patients with type 2 diabetes.Setting2011-2021.MethodsWe included both cohort studies and randomized trials that evaluated bariatric surgery added to medical therapy compared with medical therapy alone in the treatment of adult patients with type 2 diabetes. Studies must have evaluated the incidence of any microvascular complication of the disease for a period of at least 6 months. We performed our search using PubMed, Scopus, EMBASE, Web of Science, and COCHRANE Central database which was performed from inception date until March 2021. PROSPERO (CRD42021243739).ResultsA total of 25 studies (160,072 participants) were included. Pooled analysis revealed bariatric surgery to reduce the incidence of any stage of retinopathy by 71% (odds ratio [OR] .29; 95% confidence interval [CI] .10–.91), nephropathy incidence by 59% (OR .41; 95% CI 17–96), and hemodialysis/end-stage renal disease by 69% (OR .31 95% CI .20–.48). Neuropathy incidence revealed no difference between groups (OR .11; 95% CI .01–1.37). Bariatric surgery increased the odds of albuminuria regression by 15.15 (95% CI 5.96–38.52); higher odds of retinopathy regression were not observed (OR 3.73; 95% CI .29–47.71). There were no statistically significant differences between groups regarding the change in surrogate outcomes.ConclusionsBariatric surgery in adult patients with diabetes reduced the odds of any stage of retinopathy, hemodialysis/end-stage renal disease, and nephropathy composite outcome. However, its effect on many individual outcomes, both surrogates, and clinically significant, remains uncertain.     

Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study

OBJECTIVE—Prediction of type 2 diabetes based on genetic testing might improve identification of high-risk subjects. Genome-wide association (GWA) studies identified multiple new genetic variants that associate with type 2 diabetes. The predictive value of genetic testing for prediction of type 2 diabetes in the general population is unclear.RESEARCH DESIGN AND METHODS—We investigated 18 polymorphisms from recent GWA studies on type 2 diabetes in the Rotterdam Study, a prospective, population-based study among homogeneous Caucasian individuals of 55 years and older (genotyped subjects, n = 6,544; prevalent cases, n = 686; incident cases during follow-up, n = 601; mean follow-up 10.6 years). The predictive value of these polymorphisms was examined alone and in addition to clinical characteristics using logistic and Cox regression analyses. The discriminative accuracy of the prediction models was assessed by the area under the receiver operating characteristic curves (AUCs).RESULTS—Of the 18 polymorphisms, the ADAMTS9, CDKAL1, CDKN2A/B-rs1412829, FTO, IGF2BP2, JAZF1, SLC30A8, TCF7L2, and WFS1 variants were associated with type 2 diabetes risk in our population. The AUC was 0.60 (95% CI 0.57–0.63) for prediction based on the genetic polymorphisms; 0.66 (0.63–0.68) for age, sex, and BMI; and 0.68 (0.66–0.71) for the genetic polymorphisms and clinical characteristics combined.CONCLUSIONS—We showed that 9 of 18 well-established genetic risk variants were associated with type 2 diabetes in a population-based study. Combining genetic variants has low predictive value for future type 2 diabetes at a population-based level. The genetic polymorphisms only marginally improved the prediction of type 2 diabetes beyond clinical characteristics.Type 2 diabetes is a multifactorial disease caused by a complex interplay of multiple genetic variants and many environmental factors. With the recent genome-wide association (GWA) studies, the number of replicated common genetic variants associated with type 2 diabetes has rapidly increased (1–7). A total of 18 polymorphisms have been firmly replicated (1–7). It is unclear whether and how the currently known genetic variants can be used in practice, because the combined effect of these variants has not been investigated in a population-based study. Particularly, because most GWA studies were enriched for patients with a positive family history and early onset of the disease, association of these variants to type 2 diabetes risk in the general population, including elderly individuals, remains to be determined.Because complex diseases are caused by multiple genetic variants, predictive testing based on a single genetic marker will be of limited value (8,9). Simulation studies suggest that the predictive value could be improved by combining multiple common low-risk variants (10–13). Several empirical studies on the predictive value of genetic polymorphisms have been conducted before the recent GWA data were available (14–16). In a case-control study, Weedon et al. (16) showed that combining the information of three polymorphisms improved disease prediction, albeit to a limited extent. Vaxillaire et al. (15) investigated 19 polymorphisms and found that the predictive value was low compared with clinical characteristics.Genetic variants associated with risk of type 2 diabetes could potentially be useful for the prediction, prevention, and early treatment of the disease. We investigated whether combining the currently known and well-replicated genetic variants predicts type 2 diabetes in the Rotterdam Study, a prospective population-based follow-up study. We investigated whether these genetic variants improve prediction beyond clinical characteristics.     

Gastrointestinal weight loss surgery for the management of type 2 diabetes: A view from Greece

Several gastrointestinal operations of bariatric surgery, originally designed to achieve and maintain weight loss, can also induce long-term remission of type 2 diabetes mellitus as well as improve other metabolic conditions including hypertension and dyslipidaemia. Moreover, bariatric surgery is increasingly being explored for the treatment of diabetes in moderately obese and non-obese diabetic patients, with positive results. The differences observed amongst the types of bariatric surgery in better control (i.e. sleeve gastrectomy) versus full remission (i.e. Roux-en-Y gastric bypass) of diabetes postoperatively constitute a significant field of study. How surgical gastrointestinal interventions achieve these changes is of a great interest to research, and is evolving rapidly. Several studies have provided evidence that surgical procedures bypassing parts of the small intestine improve glucose homeostasis through mechanisms beyond reduced food intake and body weight. The two major hypotheses put forth to explain these mechanisms are the ‘foregut’ and the ‘hindgut’ hypothesis, focusing on the changes of the secretion pattern of gastrointestinal hormones and neuroendocrine signals observed after surgical manipulation of the gastrointestinal tract. Research to elucidate such weight-independent anti-diabetes mechanisms should facilitate the design of novel anti-diabetic gastrointestinal manipulations, devices and pharmacotherapeutics for obese and non-obese diabetic patients.     

Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.     

Association of birth weight with adult lung function: findings from the British Women's Heart and Health Study and a meta-analysis

BACKGROUND: The aim of this study was to examine the associations between birth weight and lung function in a cohort of women aged 60-79 years and to combine these results with those from other published studies in a systematic review and meta-analysis. METHODS: The associations of self-reported birth weight with adult lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and forced expiratory flow rate during mid expiration (FEF(25-75)), all measured using standard procedures, were assessed in a cross sectional study of 2257 British women aged 60-79 years. A detailed literature search was used to identify all published studies of the association, and meta-analysis was used to pool the results from our study and all published studies. RESULTS: There were positive linear associations between birth weight and all three measures of lung function in simple age and examining nurse adjusted regression models. However, with adjustment for height (squared), all three associations attenuated towards the null: adjusted (age, nurse, height2) change in FEV1 per 1 kg birth weight was 0.01 l (95% CI -0.02 to 0.04); in FVC was 0.02 l (95% CI -0.02 to 0.07), and in FEF(25-75) was 0.00 l (95% CI -0.04 to 0.04). Further adjustment for life course socioeconomic position, adult body mass index, and smoking did not alter these associations. The results were similar among life long non-smokers and those who had ever smoked. A meta-analysis of eight studies of adults suggested that there was a positive association between birth weight and FEV1: pooled increase in FEV1 per 1 kg in birth weight 0.048 l (95% CI 0.026 to 0.070) adjusted for age, smoking, and height (or height squared). There was no evidence of small study bias in this meta-analysis. CONCLUSIONS: There is a modest positive association between birth weight and lung function which indicates that intrauterine factors might have a role in lung development.     

Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the Diabetes Control and Complications Trial

Intensive therapy for type 1 diabetes results in greater weight gain than conventional therapy. Many factors may predispose to this greater weight gain, including improved glycemic control, genetic susceptibility to obesity, and hypoglycemia. To study this, relationships among family history of type 2 diabetes, frequency of severe hypoglycemia, beta-cell autoantibodies, and weight gain were examined in 1,168 subjects aged > or =18 years at baseline randomized to intensive and conventional therapy groups in the Diabetes Control and Complications Trial. With intensive therapy, subjects with a family history of type 2 diabetes had greater central weight gain and dyslipidemia characterized by higher triglyceride levels and greater cholesterol in VLDLs and intermediate-density lipoproteins compared with subjects with no family history. Neither the frequency of severe hypoglycemia nor positivity to GAD65 and insulinoma-associated protein 2 antibodies was associated with increased weight gain with either intensive or conventional therapy. These data support the hypothesis that increased weight gain with intensive therapy might be explained, in part, by genetic traits.     

The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.     

Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001-0.009, odds ratios [ORs] 1.27-1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.     

Laparoscopic sleeve gastrectomy: perioperative outcomes,weight loss and impact on type 2 diabetes mellitus over 2 years

Background

Laparoscopic sleeve gastrectomy (LSG) is an increasingly performed operation for morbid obesity worldwide. To date there has been limited experience in Canada. We report our intermediate results, assessing whether LSG can be safely performed at a Canadian academic teaching hospital and whether it is effective as a bariatric procedure and as metabolic therapy for type 2 diabetes mellitus.

Methods

We performed a retrospective review of all patients who underwent LSG at our institution from Sept. 1, 2007, to June 30, 2011.

Results

We included 166 patients (mean age 44 yr, 82% female) in our study. The mean preoperative body mass index was 49.61. At baseline, 87 (52%) patients had type 2 diabetes. For this subgroup, mean preoperative HbA1c and AC glucose were 7.6% and 8.3 mmol/L, respectively. The mean duration of surgery was 93 minutes. Major complications included 1 staple line leak (0.6%), and 2 patients required reintervention for bleeding (1.2%). The mean hospital stay was 2.6 days. Two patients required readmission (1.2%). Seven minor complications occurred (4%). Postoperative excess weight loss was 49.3% at 6 months, 54.2% at 12 months and 64.4% at 24 months. In the type 2 diabetes subgroup, resolution occurred in 78% and improvement in 7% of patients at 12 months.

Conclusion

Laparoscopic sleeve gastrectomy can be safely performed at Canadian teaching hospitals. It is effective both as a bariatric procedure and as a therapeutic intervention for type 2 diabetes mellitus.     

The comparative effects of bariatric surgery on weight and type 2 diabetes

Background: Epidemiological evidence confirms that risk of developing type 2 diabetes is related to weight gain. Weight reduction is beneficial as relative risk is reduced to 0.13 for weight loss >20 kg. This raises the question of effectiveness of bariatric surgery on 1) weight loss and 2) diabetes-related outcomes in morbidly obese patients. Methods: We reviewed the literature using Medline. Only 2 meta-analyses reporting on both outcomes were included, as well as 50 systematic reviews or primary studies. Results: Meta-analyses mainly based on case series data as well as controlled studies confirm that bariatric surgery is highly effective in obtaining weight reduction in morbidly obese patients up to 60% of the excess weight, along with resolution of preoperative diabetes in more than 75% of cases. Among bariatric surgery techniques, malabsorptive procedures (biliopancreatic diversion and gastric bypass) appear to be more effective on both outcomes than restrictive procedures (gastroplasty and gastric banding). Conclusion: Even if more studies are needed to confirm current evidence, bariatric surgery is effective for controlling diabetes. It appears as an efficient strategy from economic modeling due to savings from reduction in diabetes-related costs.     

Lamin A/C polymorphisms, type 2 diabetes, and the metabolic syndrome: case-control and quantitative trait studies

Mutations in the LMNA gene, encoding the nuclear envelope protein lamin A/C, are responsible for a number of distinct disease entities including Dunnigan-type familial partial lipodystrophy. Dunningan-type lipodystrophy is characterized by loss of subcutaneous adipose tissue, insulin resistance, dyslipidemia, and type 2 diabetes and shares many of the features of the metabolic syndrome. Furthermore, several genome-wide linkage scans for type 2 diabetes have found evidence of linkage at chromosome 1q21.2, the region that harbors the LMNA gene. Therefore, LMNA is a biological and positional candidate for type 2 diabetes susceptibility. Previous studies have reported association between a common LMNA variant (1908C>T; rs4641) and adverse metabolic traits in ethnically diverse populations from Asia and North America. In the present study, we characterized the common variation across the LMNA gene (including rs4641) and tested for association with type 2 diabetes in two large case-control studies (n = 2,052) and with features of the metabolic syndrome in a separate cohort study (n = 1,572). Despite our study being sufficiently powered to detect effects similar and even smaller in magnitude than those previously reported, none of the LMNA single nucleotide polymorphisms were statistically significantly associated with type 2 diabetes or the metabolic syndrome. Thus, it appears unlikely that variation at LMNA substantially increases the risk of type 2 diabetes or related traits in U.K. Europids.     

活性维生素D3对2型糖尿病患者肾脏保护作用的Meta分析

目的系统评价活性维生素D3治疗2型糖尿病(type 2 diabetes,T2DM)的有效性和安全性以及其对肾脏的保护作用。方法计算机检索PubMed、EMBase、谷歌学术、中国知网、维普数据库、万方数据库和中国生物医学文献数据库,检索时间范围均从建库至2014年12月。收集以活性维生素D3为干预措施治疗T2DM的临床随机对照试验(randomized controlled trials,RCT),按照Cochrane系统评价方法,对纳入标准的RCT进行方法学质量评价和疗效指标合并分析。结果共纳入10个RCT。采用固定效应模型对尿白蛋白肌酐比值(urinary albumin creatinine ratio,UACR)进行比较,加权均数差(standardized mean difference,SMD)=-0.34(95%CI:-0.55,-0.12;P=0.002),治疗组较对照组明显降低;采用随机效应模型对血肌酐进行比较:SMD=-1.27(95%CI:-3.66,1.12;P=0.30),差异无统计学意义(P0.05);另外,治疗组在降低T2DM患者胰岛素抵抗、三酰甘油、总胆固醇、收缩压和升高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)等方面效果与对照组比较[SMD或加权均数差(weighted mean difference,WMD)(95%CI)分别为-2.69(-3.42,-1.97);-0.37(-0.63,-0.11);-0.30(-0.56,-0.05);-5.94(-9.08,-2.80);0.33(0.03,0.63)],差异有统计学意义(P0.05);但对糖化血红蛋白(glycosylated hemoglobin,HbA1c)和舒张压无明显影响[WMD(95%CI)分别为0.06(-0.08,0.19),-1.77(-3.65,-0.12);P0.05]。结论活性维生素D3可以改善T2DM患者糖代谢,降低血脂、血压及蛋白尿,具有一定的肾脏保护作用。     

The effects of metabolic surgery on microvascular complications in obese patients with type 2 diabetes: a meta-analysis

BackgroundMetabolic surgery is a standard treatment for obesity with type 2 diabetes (T2D), although the effects of metabolic surgery on the incidence rate of microvascular complications remain controversial.ObjectivesWe aimed to evaluate the effect of metabolic surgery versus nonsurgical treatments on the incidence rate of microvascular complications in obesity with T2D.SettingA meta-analysis of published studies.MethodsWe searched PubMed, Web of Science, and the Cochrane Library to identify clinical studies assessing the effect of metabolic surgery on the incidence rate of microvascular diabetic complications compared with that of nonsurgical treatments. We extracted the primary outcomes, including the incidence rate of microvascular complications after metabolic surgery.ResultsA total of 32,756 participants from 12 studies were identified. Metabolic surgery reduced the incidence rate of microvascular complications (odds ratios [OR], .34; 95% confidence intervals [CI], .30–.39; P < .001) compared with that of nonsurgical treatments in obesity with T2D. Moreover, metabolic surgery also reduced the incidence of diabetic nephropathy (OR, .39; 95% CI, .30–.50; P < .001), diabetic retinopathy (OR, .52; 95% CI, .42–.65; P < .001) and diabetic neuropathy (OR, .27; 95% CI, .22–.34; P < .001) compared with nonsurgical treatments in obesity with T2D.ConclusionMetabolic surgery was superior to nonsurgical treatments in reducing the incidence of microvascular complications in obesity with T2D. Prospective studies, preferably randomized controlled trials, with evaluations of different types of metabolic surgery are warranted to provide guidelines for treatment preferences in obesity with T2D.