Diabetes epidemic sweeping the Arab world

The prevalence of type-2 diabetes mellitus(T2DM) has increased dramatically during the last 2 decades, a fact driven by the increased prevalence of obesity, the primary risk factor for T2 DM. The figures for diabetes in the Arab world are particularly startling as the number of people with diabetes is projected to increase by 96.2% by 2035. Genetic risk factors may play a crucial role in this uncontrolled raise in the prevalence of T2 DM in the Middle Eastern region. However, factors such as obesity, rapid urbanization and lack of exercise are other key determinants of this rapid increase in the rate of T2 DM in the Arab world. The unavailability of an effective program to defeat T2 DM has serious consequences on the increasing rise of this disease, where available data indicates an unusually high prevalence of T2 DM in Arabian children less than 18 years old. Living with T2 DM is problematic as well, since T2 DM has become the 5th leading cause of disability, which was ranked 10 th as recently as 1990. Giving the current status of T2 DM in the Arab world, a collaborative international effort is needed for fighting further spread of this disease.     

Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population

Type 1 diabetes mellitus(T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1 DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1 DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1 DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1 DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.     

不同阶段2型糖尿病诱发骨质疏松症的致病机制研究进展

大量临床研究表明,2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨折风险明显增加。因此,T2DM诱发的骨质疏松症(osteoporosis,OP)被认为是最严重的糖尿病并发症之一。骨脆性增加是糖尿病性骨质疏松症(diabetic osteoporosis,DOP)的典型特征,其发病机制是多因素引起的,包括肥胖、高胰岛素血症、高血糖(hyperglycemia,HG)、晚期糖基化终产物(advanced glycation end products,AGEs)积聚和氧化产物积累以及微血管病变的存在等。这些因素在T2DM不同时期是相互平衡或相互促进的,而肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)等炎症因子的异常活化打破了骨形成和骨吸收的代谢平衡,导致骨脆性增加。骨强度和骨折风险的变化取决于疾病进展的阶段。因此,糖尿病骨病的病理生理变化可以通过分别考虑糖尿病早期和晚期骨骼相关因素来广泛讨论,其中早期阶段以胰岛素抵抗和高胰岛素血症为特征,这些因素会导致糖尿病发病和初始阶段的骨密度(bone mineral density,BMD)增加。而晚期阶段的特征是β细胞衰竭,AGEs和氧化产物的堆积,加速衰老和血管并发症的发展。为此,本文希望对T2DM的不同阶段与骨代谢的关系进行综述,以便更好的认识T2DM的进展加速骨脆性风险的病理过程和致病机制,为治疗T2DM和T2DM诱发的OP、降低T2DM患者骨折发生的风险发挥积极的作用。     

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.     

Fatty liver disease in diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM), likely reflecting the frequent occurrence of obesity and insulin resistance in T2DM. NAFLD also can occur in type 1 DM (T1DM), but must be distinguished from the more common glycogen hepatopathy as a cause of hepatomegaly and liver function abnormalities in T1DM. Weight reduction achieved by diet and exercise is effective in preventing and treating NAFLD in obese diabetic subjects. Bariatric surgery also has been shown to reverse NAFLD in T2DM, and recently approved weight loss medications should be evaluated for their impact on the development and progression of NAFLD. There is limited evidence suggesting that specific drugs used for blood glucose control in T2DM [thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) analogs, and dipeptidyl peptidase-4 (DPP-4) inhibitors] and also statins may have a role in preventing or treating NAFLD in patients with diabetes.     

Diabetic kidney disease in pediatric patients: A current review

In the last decades, a significant increase in the incidence of diabetic kidney disease (DKD) was observed concomitant with rising diabetes mellitus (DM) incidence. Kidney disease associated with DM in children and adolescents is represented by persistent albuminuria, arterial hypertension, progressive decline in estimated glomerular filtration rate to end-stage renal disease and increased cardiovascular and all-cause morbidity and mortality of these conditions. In medical practice, the common and still the “gold standard” marker for prediction and detection of diabetic kidney involvement in pediatric diabetes is represented by microalbuminuria screening even if it has low specificity to detect early stages of DKD. There are some known limitations in albuminuria value as a predictor biomarker for DKD, as not all diabetic children with microalbuminuria or macroalbuminuria will develop end-stage renal disease. As tubular damage occurs before the glomerular injury, tubular biomarkers are superior to the glomerular ones. Therefore, they may serve for early detection of DKD in both type 1 DM and type 2 DM. Conventional and new biomarkers to identify diabetic children and adolescents at risk of renal complications at an early stage as well as renoprotective strategies are necessary to delay the progression of kidney disease to end-stage kidney disease. New biomarkers and therapeutic strategies are discussed as timely diagnosis and therapy are critical in the pediatric diabetic population.     

Diabetes remission after bariatric surgery

Over the last decade, obesity rates have continued to rise in the United States as well as worldwide and are showing no signs of slowing down. This rise is in parallel with the increasing rates of type 2 diabetes mellitus (T2DM). Given the association between obesity and T2DM and their strong correlation with increased morbidity and mortality in addition to healthcare expenditure, it is important to recognize the most effective ways to combat them. Thus, we performed a review of literature that focused on assessing the outcomes of T2DM following bariatric surgery. Available evidence suggests that bariatric surgery provides better T2DM resolution in obese patients when compared to best medical management alone. Additionally, Biliopancreatic diversion with duodenal switch as well as Roux-en-Y gastric bypass have demonstrated higher rates of T2DM resolution when compared with other bariatric procedures.     

Pediatric aspects of diabetic kidney disease

Type 1 diabetes mellitus (DM1) commonly occurs in childhood, although many pediatric centers are now seeing more cases of type 2 diabetes (DM2). Kidney failure caused by either type of diabetes is uncommon during childhood, but these years of hyperglycemia contribute to long-term complications. All children with diabetes warrant screening of glomerular filtration rate, blood pressure, and urine albumin excretion. Screening should begin after 5 years of DM1 or at puberty. A similar screening strategy should start at the time of diagnosis of DM2. Atypical features such as dipstick positive proteinuria or active urine sediment may warrant referral to a nephrologist for evaluation, including biopsy. The first line of treatment in either form of diabetes is achieving the best glycemic control possible. Patients developing microalbuminuria or hypertension should receive antiangiotensin II drugs. Adult studies suggest blood pressure goals should be lower in diabetes than in the general population. Although direct evidence is not yet available in children, achieving blood pressure below the 90th percentile for age, height, and gender seems prudent. Longitudinal studies and new screening tests may allow detection of susceptible children earlier in the course of DM1 or DM2, perhaps allowing prevention of diabetic kidney disease.     

Sugar intake from sweetened beverages and diabetes: A narrative review

Type 2 diabetes mellitus (T2DM) is one of the fastest growing public health concerns around the world. Sugar-sweetened beverage (SSB) consumption has been proven to be associated with adverse health consequences in the diabetic population. Reducing SSB consumption, body weight control, healthy diets, and increased physical activity have been suggested as strategies to improve diabetes prevention and management. This literature review provides an overview of: (1) The association between SSB consumption and the risk of T2DM; (2) Types of SSB consumption and T2DM; (3) The effect of obesity and inflammation on the association between SSB consumption and risk of T2DM; and (4) SSB consumption in T2DM patients. There is still work to be done to determine how SSB consumption is related to T2DM, but the current research on identifying the association between SSB consumption and T2DM is promising, with the most promising studies confirming the connection between SSBs, T2DM risk, and diabetes management. Future studies should explore more effective SSB related diabetes prevention and management interventions.     

β-cell dysfunction: Its critical role in prevention and management of type 2 diabetes

Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2 DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cell dysfunction is present at the diagnosis of T2 DM and progressively worsens with disease duration. β-cell dysfunction is associated with worseningof glycemic control and treatment failure; thus, it is important to preserve or recover β-cell functional mass in the management of T2 DM. Since β-cell regenerative capacity appears somewhat limited in humans, reducing β-cell workload appears to be the most effective way to preserve β-cell functional mass to date, underpinning the importance of lifestyle modification and weight loss for the treatment and prevention of T2 DM. This review summarizes the current knowledge on β-cell functional mass in T2 DM and discusses the treatment strategy for T2 DM.     

Metabolic surgery: A paradigm shift in type 2 diabetes management

Obesity and type 2 diabetes mellitus (T2DM) are major public health issues globally over the past few decades. Despite dietary interventions, lifestyle modifications and the availability of several pharmaceutical agents, management of T2DM with obesity is a major challenge to clinicians. Metabolic surgery is emerging as a promising treatment option for the management of T2DM in the obese population in recent years. Several observational studies and a few randomised controlled trials have shown clear benefits of various bariatric procedures in obese individuals in terms of improvement or remission of T2DM and multiple other health benefits such as improvement of hypertension, obstructive sleep apnoea, osteoarthritis and non-alcoholic fatty liver disease. Uncertainties about the long-term implications of metabolic surgery such as relapse of T2DM after initial remission, nutritional and psychosocial complications and the optimal body mass index for different ethnic groups exist. The article discusses the major paradigm shift in recent years in the management of T2DM after the introduction of metabolic surgery.     

Perioperative management of pediatric surgical patients with diabetes mellitus

Pediatric patients with diabetes are managed with increasingly complex regimens. To optimally manage these patients during the perioperative period, pediatric anesthesiologists must carefully consider the pathophysiology of the disease, patient-specific methods of treatment, status of glycemic control, and the type of surgery proposed. Important pediatric issues, including body size, pubertal development, and ability to tolerate nil per os status, must be considered. To keep pace with the array of options for treating diabetes in children, the perioperative plan should be developed in consultation with a pediatric endocrinologist. We present an algorithm that was developed at Children's Hospital Boston for the management of pediatric patients with either type 1 or type 2 diabetes mellitus presenting for surgery and general anesthesia. This collaborative effort between the pediatric anesthesia and endocrine services represents one example of a standardized approach to these patients that should facilitate care and improve management. Differences from previously published recommendations are highlighted, as are expected changes caused by the continued evolution of pediatric diabetes care. IMPLICATIONS: The evolution of diabetes care for children has made the management of perioperative blood glucose levels a greater challenge for pediatric anesthesiologists. A standardized algorithm for the perioperative management of pediatric patients with type 1 or type 2 diabetes mellitus os presented.     

Diabetic nephropathy in children and adolescents

Type 1 diabetes mellitus (T1DM) commonly occurs in childhood or adolescence, although the rising prevalence of type 2 diabetes mellitus (T2DM) in these age groups is now being seen worldwide. Diabetic nephropathy (DN) develops in 15–20% of subjects with T1DM and in similar or higher percentage of T2DM patients, causing increased morbidity and premature mortality. Although overt DN or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to microalbuminuria or incipient DN. Therefore, all diabetics warrant ongoing assessment of kidney function and screening for the earliest manifestations of renal injury. Pediatric health care professionals ought to understand about risk factors, strategy for prevention, method for screening, and treatment of early DN. This review considers each form of diabetes separately, including natural history, risk factors for development, screening for early manifestations, and strategy recommended for prevention and treatment of DN in children and adolescents.     

State of art on the mechanisms of laparoscopic sleeve gastrectomy in treating type 2 diabetes mellitus

Obesity and type-2 diabetes mellitus (T2DM) are metabolic disorders. Obesity increases the risk of T2DM, and as obesity is becoming increasingly common, more individuals suffer from T2DM, which poses a considerable burden on health systems. Traditionally, pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and all-cause mortality and to increase life expectancy. Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity, especially in patients with refractory obesity, owing to its many benefits including good long-term outcomes and almost no weight regain. The bariatric surgery options have markedly changed recently, and laparoscopic sleeve gastrectomy (LSG) is gradually gaining popularity. LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity, with a high cost-benefit ratio. Here, we review the me-chanism associated with LSG treatment of T2DM, and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones, gut microbiota, bile acids, and adipokines to clarify current treatment modalities for patients with obesity and T2DM.     

Clinical pharmacology of antidiabetic drugs: What can be expected of their use?

The pharmacotherapy of type 2 diabetes mellitus (T2DM) has markedly evolved in the last two decades. Classical antidiabetic agents (sulphonylureas, metformin, insulin) are now in competition with new glucose-lowering medications. Alpha-glucosidase inhibitors and thiazolidinediones (glitazones) were not able to replace older agents, because of insufficient efficacy and/or poor tolerability/safety. In contrast, incretin-based therapies, both dipeptidyl peptidase-4 inhibitors (DPP-4is or gliptins, oral agents) and glucagon-like peptide-1 receptor agonists (GLP-1RAs, subcutaneous injections) are a major breakthrough in the management of T2DM. Because they are not associated with hypoglycaemia and weight gain, DPP-4is tend to replace sulphonylureas as add-on to metformin while GLP-1RAs tend to replace basal insulin therapy after failure of oral therapies. Furthermore, placebo-controlled cardiovascular outcome trials demonstrated neutrality for DPP-4is, but cardiovascular protection for GLP-1RAs in patients with T2DM at high cardiovascular risk. More recently sodium-glucose cotransporter 2 inhibitors (SGLT2is or gliflozins, oral agents) also showed cardiovascular protection, especially a reduction in hospitalization for heart failure, as well as a renal protection in patients with and without T2DM, at high cardiovascular risk, with established heart failure and/or with chronic kidney disease. Thus, GLP-1RAs and SGLT2is are now considered as preferred drugs in T2DM patients with or at high risk of atherosclerotic cardiovascular disease whereas SGLT2is are more specifically recommended in patients with or at risk of heart failure and renal (albuminuric) disease. The management of T2DM is moving from a glucocentric approach to a broader strategy focusing on all risk factors, including overweight/obesity, and to an organ-disease targeted personalized approach.     

Development of therapeutic options on type 2 diabetes in years:Glucagon-like peptide-1 receptor agonist's role intreatment; from the past to future

Diabetes mellitus(DM) is a chronic metabolic disease characterized by hyperglycemia. Type 2 diabetes(T2 DM) accounting for 90% of cases globally. The worldwide prevalence of DM is rising dramatically over the last decades, from 30 million cases in 1985 to 382 million cases in 2013. It's estimated that 451 million people had diabetes in 2017. As the pathophysiology was understood over the years, treatment options for diabetes increased. Incretin-based therapy is one of them. Glucagon-like peptide-1 receptor agonist(GLP-1 RA) not only significantly lower glucose level with minimal risk of hypoglycemia but also, they have an important advantage in themanagement of cardiovascular risk and obesity. Thus,we will review here GLP-1 RAsrole in the treatment of diabetes.     

多学科综合治疗肥胖症合并2型糖尿病

2型糖尿病常合并肥胖症、高血压、高血脂等代谢综合征症候群。对于此类难以控制的2型糖尿病合并肥胖症的诊断和治疗，内科常用非手术如控制饮食、运动、药物方式治疗；外科则可采用手术方式，改善2型糖尿病及其代谢综合征症候群，达到“治愈”糖尿病和高脂血症的目的。中南大学湘雅三医院对1例肥胖症合并2型糖尿病患者采用多学科协作综合治疗模式，取得了较好疗效。     

Type 2 diabetes mellitus in children and adolescents

Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.     

Update on cystic fibrosis-related diabetes

Diabetes mellitus has emerged as a common comorbidity in cystic fibrosis and is considered a clinical entity (cystic fibrosis-related diabetes, CFRD) distinct from that of type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The relevance of this diagnosis extends not only from its imposition of additional medical burden but its association with worse health outcomes in individuals with CF. This paper will review the 2010 U.S. and other international guidelines for screening and treating CFRD. It will highlight newer data regarding early glucose and insulin secretion defects, mechanisms linking CFRD to worse outcomes, and recent advances in T2DM that may provide insights for CFRD; insulin secretion will be reviewed as background for these recent developments.     

Association of β-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children

BACKGROUNDIn addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM.AIMTo investigate the association of β-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODSThis multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the β-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile.RESULTSThe male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40–11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60–2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSIONBesides insulin resistance, β-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.