Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Effects of exercise training on mitochondrial function in patients with type 2 diabetes

Type 2 diabetes is characterized by a decreased ability of insulin to facilitate glucose uptake into insulin sensitive tissue,i.e.,skeletal muscle.The mechanism behind this is at the moment unresolved.It has been suggested that increased amount of lipids inside the skeletal muscle(intramuscular triglyceride,diacylglycerol and ceramides)will impair insulin action in skeletal muscle,but data are not consistent in the human literature.It has also been hypothesized that the impaired insulin sensitivity is due to a dysfunction in the mitochondria resulting in an impaired ability to oxidize lipids,but the majority of the literature is not supporting this hypothesis.Recently it has been suggested that the production of reactive oxygen species play an essential role in skeletal muscle insulin sensitivity.It is well accepted that physical activity(endurance,strength and high intensity training)improves insulin sensitivity in healthy humans and in patients with type 2 diabetes.Whether patients with type 2 diabetes have the same beneficial effects(same improvement)as control subjects,when it comes to regular physical activity in regard to mitochondrial function,is not established in the literature.This review will focus only on the effect of physical activity on skeletal muscle(mitochondrial function)in patients with type 2 diabetes.     

WJD 5~(th) Anniversary Special Issues(3): Type 1 diabetes Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Inflammation in diabetic kidney disease

Diabetes mellitus entails significant health problems worldwide.The pathogenesis of diabetes is multifactorial,resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events,with metabolic and hemodynamic alterations.In this context,inflammation has emerged as a key pathophysiology mechanism.New pathogenic pathways will provide targets for prevention or future treatments.This review will focus on the implications of inflammation in diabetes mellitus,with special attention to inflammatory cytokines.     

WJD 5~h Anniversary Special Issues(1):Insulin Insulin and bone:Recent developments

While insulin-like growth factorⅠis a well-known anabolic agent in bone evidence is beginning to accumulate that its homologue,insulin,also has some anabolic properties for bone.There is specific evidence that insulin may work to stimulate osteoblast differentiation,which in turn would enhance production of osteocalcin,the osteoblast-produced peptide that can stimulate pancreaticβcell proliferation and skeletal muscle insulin sensitivity.It is uncertain whether insulin stimulates bone directly or indirectly by increasing muscle work and therefore skeletal loading.We raise the question of the sequence of events that occurs with insulin resistance,such as type 2 diabetes.Evidence to date suggests that these patients have lower serum concentrations of osteocalcin,perhaps reduced skeletal loading,and reduced bone strength as evidenced by microindentation studies.     

WJD 5~(th) Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue.Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue,which leads to replenishment of recipients’white adipose tissue;increase of a number of beneficial adipokines;and fast and long-lasting euglycemia.Insulin-independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions,and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models.While the underlying mechanisms are not fully documented,the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported,and are worthy of attention as a powerful tool in combating metabolic disease.     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Structured SMBG in early management of T2DM: Contributions from the St Carlos study

Diabetes mellitus type 2(T2DM)is a global pandemic that will affect 300 million people in the next decade.It has been shown that early and aggressive treatment of T2DM from the onset decreases complications,and the patient’s active role is necessary to achieve better glycemic control.In order to achieve glycemic control targets,an active attitude in patients is needed,and selfmonitoring of blood glucose(SMBG)plays a significant role.Nowadays,SMBG has become an important component of modern therapy for diabetes mellitus,and is even more useful if it is performed in a structured way.SMBG aids physicians and patients to achieve a specific level of glycemic control and to prevent hypoglycemia.In addition,SMBG empowers patients to achieve nutritional and physical activity goals,and helps physicians to optimize the different hypoglycemic therapies as demonstrated in the St Carlos study.This article describes the different ways of using this educational and therapeutic tool from the medical point of view as well as from the patient’s perspective.     

Management of type 2 diabetes mellitus in youth

The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus(T2DM) in this age group.However,there are limited data on the efficacy of different antidiabetic agents in youth.In this context,the Treatment Options for Type 2 Diabetes in Adolescents and Youth trial recently reported that the majority of obese children and adolescents 10-17-years old with newly diagnosed T2DM(T2DM duration less than 2 years) could not achieve HbA1c levels < 8% for more than 1 year with metformin monotherapy,metformin plus rosiglitazone combination,or metformin and lifestyle changes.These findings suggest that,in the majority of youth with T2DM,tight long-term glycemic control with oral agents is an elusive goal and that most patients will require treatment with insulin within a few years of diagnosis to achieve HbA1c targets and reduce the risk of macroand microvascular complications.Therefore,reducing the incidence of T2DM by preventing pediatric obesity through the implementation of lifestyle changes in the community should be the primary objective of healthcare systems.     

Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.     

我国2型糖尿病的外科治疗术式探讨

由于我国的2型糖尿病患者中位体质量指数（BMI）只有24 kg/m2以及我国糖尿病患者存在的饮食差异性,使得目前国内尚缺少充足的减重手术数据和指南,因此,我国医生在国际上公认的术式之外,进行了手术治疗2型糖尿病的术式探索.2011年国际糖尿病联盟（IDF）治疗2型糖尿病的推荐术式主要有：胃旁路手术（GBP）、袖状胃切除术（SG）、胆胰转流手术（BPD）、十二指肠转位术（DS）和可调节胃束带术（AGB）.本文重点分析我国外科医生的进展探索性术式,主要包括：袖状胃切除术加十二指肠空肠旁路术,十二指肠空肠旁路术,袖状胃切除加空回肠旁路术,袖状胃切除加回肠间置术,单纯回肠间置术及空、回肠短路术,胃大弯折叠术以及折叠术加胃束带术,以及其他在内镜下完成的减重术式.每种术式均各有特点,但哪种术式更为适合国内2型糖尿病患者,尚需临床的长期随访及大样本的多中心研究的开展,相信在科学规范前提下,我国的外科医生会摸索出最适合本国2型糖尿病患者的手术方式.     

Psychosocial factors affecting the etiology and management of type 1 diabetes mellitus: A narrative review

Type 1 diabetes (T1D) is one of the most common chronic diseases in children and adolescents worldwide. Its etiopathogenesis results from the interplay of genetic and environmental variables. Among the latter, psychological stress has been implicated in disease onset as well as disease management. Various studies, including large population-based studies, have highlighted the role of stressful life events in the etiopathogenesis of T1D. In this article, we also emphasize the importance of attachment in the early child-caregiver relationship, which can be seen as a measure of the quality of the relationship and is crucial for stress and emotional regulation. It serves as a model for all subsequent relationships in one’s life. We summarize some of the few studies performed in the field of attachment and T1D etiopathogenesis or management. T1D management demands a lifelong therapeutic regimen to prevent acute and chronic complications. In addition to psychological stress, psychological factors such as family functioning, developmental adjustment, autonomy, mental health problems and other factors have been found to relate to metabolic control. Psychological factors need to be understood not as a single directional causality-based principle but as a dynamic bi- or multidirectional system that is affected by the normal developmental transitions of childhood and adolescence.     

双能X线骨密度仪测定83例2型糖尿病人骨密度分析

目的 了解2型糖尿病患腰椎及髋部骨矿物密度的变化。方法 双能X线骨密度仪测定2型糖尿病病人共83例(年龄40—79岁)，其中男性43例，女性40例；健康对照组71例(年龄40—79岁)，男性38例，女性33例。对比分析糖尿病组与同性别同龄正常组的测量结果，另根据病程将糖尿病组分为大于5年及小于5年组，并对2组结果进行分析。结果①糖尿病组与健康对照组比较，腰椎及髋部骨密度差异无显性；②病程大于5年与小于5年的2型糖尿病患间骨密度差异无显性。结论 2型糖尿病是否引起骨矿物密度降低或增高有待进一步研究。     

胃转流术治疗2型糖尿病的临床疗效：附214例报告

目的 Roux-en-Y式胃转流术（RY-GBP）是2型糖尿病患者接受外科手术治疗的主要术式之一。本研究旨在进一步验证RY-GBP的手术治疗效果。方法 214例2型糖尿病（T2DM）患者均行RY-GBP术,术中根据体质指数和胰岛素抵抗情况,选择合适的残胃（Pouch）容积和空肠袢长度。患者于术前和术后3,6,12个月行OGTT试验,并测定空腹血清胰岛素（FIns）、空腹血清C肽（FC-P）、糖化血红蛋白（HbAlc）、体重指数（BMI）,密切关注患者术后的降糖药服用情况及糖尿病并发症改善情况。结果 214例患者中,51例（23.8%）术后出院时即达治愈标准,停用降糖药物,78例（36.4%）于术后0～3个月内停药,21例（9.8%）于术后3～6个月内停药,18例（8.4%）于术后6～12个月内停药。另外46例（21.5%）12个月后仍服用降糖药物,但药物剂量有不同程度地减少,尚在进一步观察中。上述病例在术后3,6,12个月的各项检测指标均有所改善,近期治愈率达78.5%（168/214）。本组无死亡病例,相关并发症包括吻合口出血2例,吻合口溃疡7例,胃瘫21例,营养不良3例,贫血8例,在给予相应治疗后均缓解。结论 RY-GBP胃转流术对肥胖型和非肥胖型2型糖尿病均有良好治疗效果,对非肥胖型2型糖尿病的治疗效果更值得进一步深入研究。     

Admission hemoglobin level and prognosis of type 2 diabetes mellitus and possible confounding factors: Correspondence

This letter to editor discusses on the publication on admission hemoglobin level and prognosis of type 2 diabetes mellitus. A comment on published article is raised. The specific confounding conditions on the hemoglobin level are mentioned. Concerns on clinal application are raised and discussed.     

Multi-omics: Opportunities for research on mechanism of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a burdensome global disease. In-depth understanding of its mechanism will help to optimize diagnosis and treatment, which reduces the burden. Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease. In the past two decades, the study of multi-omics on T2DM-related intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs. The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies. The use of metagenomics, 16S RNA sequencing, and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions. Lipidomics combined with other “omics” has characterized lipid metabolism disorders in T2DM. The combined application and cross-validation of multi-omics can screen for dysregulation in T2DM, which will provide immense opportunities to understand the mechanisms behind T2DM.     

Association of obesity with hypertension and type 2 diabetes mellitus in India: A meta-analysis of observational studies

AIM To perform a meta-analysis of the association of obesity with hypertension and type 2 diabetes mellitus(T2DM) in India among adults. METHODS To conduct meta-analysis, we performed comprehensive, electronic literature search in the PubM ed, CINAHL Plus, and Google Scholar. We restricted the analysis to studies with documentation of some measure of obesity namely; body mass index, waist-hip ratio, waist circumference and diagnosis of hypertension or diagnosis of T2DM. By obtaining summary estimates of all included studies, the meta-analysis was performed using both RevM an version 5 and "metan" command STATA version 11. Heterogeneity was measured by I~2 statistic. Funnel plot analysis has been done to assess the study publication bias.RESULTS Of the 956 studies screened, 18 met the eligibility criteria. The pooled odds ratio between obesity and hypertension was 3.82(95%CI: 3.39 to 4.25). The heterogeneity around this estimate(I~2 statistic) was 0%, indicating low variability. The pooled odds ratio from the included studies showed a statistically significant association between obesity and T2DM(OR = 1.14, 95%CI: 1.04 to 1.24) with a high degree of variability.CONCLUSION Despite methodological differences, obesity showed significant, potentially plausible association with hypertension and T2DM in studies conducted in India. Being a modifiable risk factor, our study informs setting policy priority and intervention efforts to prevent debilitating complications.     

Literature review of type 2 diabetes mellitus among minority Muslim populations in Israel

This review surveys the literature published on the characteristics and implications of pre-diabetes and type 2 diabetes mellitus(T2DM) for the Arab andBedouin populations of Israel. T2 DM is a global health problem. The rapid rise in its prevalence in the Arab and Bedouin populations in Israel is responsible for their lower life expectancy compared to Israeli Jews. The increased prevalence of T2 DM corresponds to increased rates of obesity in these populations. A major risk group is adult Arab women aged 55-64 years. In this group obesity reaches 70%. There are several genetic and nutritional explanations for this increase. We found high hospitalization rates for micro and macrovascular complications among diabetic patients of Arab and Bedouin origin. Despite the high prevalence of diabetes and its negative health implications, there is evidence that care and counseling relating to nutrition, physical activity and self-examination of the feet are unsatisfactory. Economic difficulties are frequently cited as the reason for inadequate medical care. Other proposed reasons include faith in traditional therapy and misconceptions about drugs and their side effects. In Israel, the quality indicators program is based on one of the world’s leading information systems and deals with the management of chronic diseases such as diabetes. The program’s baseline data pointed to health inequality between minority populations and the general population in several areas, including monitoring and control of diabetes. Based on these data, a pilot intervention program was planned, aimed at minority populations. This program led to a decrease in inequality and served as the basis for a broader, more comprehensive intervention that has entered the implementation stage. Interventions that were shown to be effective in other Arabic countries may serve as models for diabetes management in the Arab and Bedouin populations in Israel.