Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.     

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.     

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.     

Diabetes and fragility fractures — A burgeoning epidemic?

Diabetes and osteoporosis are both diseases of epidemic proportions whose incidence is increasing worldwide. The etiology of osteoporosis is multifactorial and may differ for type 1(T1DM) as compared to type 2 (T2DM). Fragility fractures are common to both types of diabetes with hip fractures occurring more frequently in the elderly T2DM population. The use of oral PPAR gamma agonists in the treatment of T2DM has also added to the risk of fracture. This perspective discusses the etiologies and issues relating to the association of diabetes with osteoporosis and fractures and suggests some theories to clarify the underlying pathophysiology. Unfortunately at this time treatment for osteoporosis and fractures remains empirical.     

New therapeutic approaches for type 1 diabetes: Disease-modifying therapies

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus (T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production (a consequence of β-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent β-cell destruction. T1DM patients with better β-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting β cells are usually lost. Therefore, to maximize the salvageable β-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Disease-modifying therapies, such as immuno- and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.     

Can a Protocol for Glycaemic Control Improve Type 2 Diabetes Outcomes After Gastric Bypass?

Background  

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for patients with type 2 diabetes (T2DM). Tight glycaemic control immediately after RYGB for T2DM may improve long-term glycaemic outcomes, but is also associated with a higher risk of hypoglycaemia. We designed a treatment algorithm to achieve optimal glycaemic control in patients with insulin-treated T2DM after RYGB and evaluated its feasibility, safety and efficacy.     

Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes

Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes(T1DM).Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes,a cause-effect relationship is less clear in T1 DM.Although endothelial dysfunction(ED) precedes atherosclerosis,it is not clear weather,in recent onset T1 DM,it may progress to clinical macrovascular disease.Moreover,endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control,long-term exercise training and use of statins.Acute,long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1 DM.The pathogenesis of endothelial dysfunction is closely related to oxidative-stress.NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells,thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation,a potent oxidant agent.Moreover,oxidative stress also uncouples endothelial nitric oxide synthase,which becomes dysfunctional,inducing formation of superoxide.Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products.Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1 DM.     

Intermittent energy restriction in type 2 diabetes: A short discussion of medication management

AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.     

Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling, resulting in glucose uptake defect, and an increased blood sugar level. Pancreatic beta cells thus enhance insulin production to compensate. This situation may cause further beta cell dysfunction and failure, which can lead diabetes mellitus(DM). Insulin resistance is thus an important cause of the development of type 2 DM. Insulin resistance has also been found to have a strong relation...     

Critical review of bone health,fracture risk and management of bone fragility in diabetes mellitus

The risk of fracture is increased in both type 1 diabetes mellitus(T1DM) and type 2 diabetes mellitus(T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.     

Enterovirus and type 1 diabetes: What is the matter?

A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.     

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus (T1DM). Fear of hypoglycemia (FoH) is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity (e.g., cardiometabolic health, improved body composition, cardiovascular fitness, quality of life). Technological advances, improved insulin regimens, and a better understanding of the physiology of various types of exercise could help ameliorate FoH. This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.     

Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah

AIM To measure the incidence and determinants(predictors) of hypoglycemia among patients with type 2 diabetes mellitus(T2DM) who were on insulin treatment for at least one year. METHODS The present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo(from 15~(th) of April, 2013 to 15~(th) of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.RESULTS The incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mildhypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.CONCLUSION Hypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.     

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.     

Co-occurrence of type 1 diabetes mellitus and celiac disease

The co-occurrence of celiac disease(CD) and type 1 diabetes(T1DM) has been reported as 5-7 times more prevalent than CD alone.The clinical presentation and natural history of CD in patients with T1 DM may vary considerably.Less than 10% of patients with T1 DM and CD show gastrointestinal symptoms.Therefore,experts support screening for CD in T1 DM patients,though there is no consensus as to the recommended frequency of screening.When stratified by time since CD diagnosis,longer follow-up and coexistence of CD are associated with significant increased risk of diabetic associated morbidity and mortality.Early CD diagnosis and treatment with a gluten-free diet are essential.     

Remission of type 2 diabetes after Roux-en-Y gastric bypass is associated with greater weight loss

BackgroundPhysiologic studies in rodents and preliminary human studies have suggested that Roux-en-Y gastric bypass (RYGB) improves type 2 diabetes mellitus (T2DM) by way of metabolic changes, long before the bariatric or weight loss effects occur, leading to the concept of “metabolic surgery.” To test this hypothesis, we studied patients with insulin-dependent T2DM who underwent RYGB to determine whether T2DM remission in this treatment-resistant subgroup occurred independent of weight loss.MethodsOf all the patients undergoing RYGB from 2000 to 2006 (n = 1546) with ≥12 months of follow-up, 318 had T2DM (21%), and 75 (24%) of these were insulin dependent. Of the 75 patients, 4 were found to have T1DM (5.3%) and were excluded, leaving a study population of 71 patients. The patients who achieved remission, defined as a cessation of diabetic medications with a hemoglobin A1c level of <7%, were compared with those who did not achieve remission. Statistical significance was set at P < .05, using the Student t test, chi-square test, and logistic regression analysis, as appropriate.ResultsAfter RYGB, all 71 patients with insulin-dependent T2DM had achieved a reduction in the dose and/or number of medications at 29.6 ± 17.0 months. Of these 71 patients, 35 (49%) demonstrated a remission of T2DM. The preoperative body mass index, age, number of medications, and hemoglobin A1c level did not differentiate between those who attained remission and those who still required diabetic medication. From the multivariate analysis, the significant factors associated with remission were the preoperative insulin dose and the percentage of excess weight loss. The percentage of excess weight loss was greater in the remission patients as early as 3 months postoperatively (P = .04) and also at 6, 12, 18, and 24 months.ConclusionRYGB uniformly improved the medication requirements of patients with insulin-dependent T2DM. Although physiologic mechanisms likely contributed, early rapid weight loss was associated with the remission of T2DM.     

纠结的成长——学习意志力的培养

初中阶段的学生往往学习意志不强,有好的想法但是由于种种原因不能很好地坚持,导致计划执行不到位,影响学业的进步。在初二学业分化的阶段,这种情况对学生影响更为严重。如何让学生自己认识到意志的重要性,并且找到改变的动力和方法,是一个急需解决的问题。所以本节课里我通过具体情境的设计,以未来成长为导向,情感体验为核心,让学生充分认识到意志力提升的价值,并且从自己和身边朋友的经验里获得启示,找到提升意志力的方向。     

Eating disorders in adolescents with type 1 diabetes:Challenges in diagnosis and treatment

Eating disorders(ED) are characterized by a persistent disturbance of eating that impairs health or psychosocial functioning.They are associated with increased rates of medical complications and mortality.Insulin omission is a unique purging behavior available to individuals with type 1 diabetes mellitus(T1DM).The standard treatment regimen for T1 DM requires a major focus on food andeating patterns.Moreover,intensive insulin therapy is associated with increasing body weight.These factors,combined with the psychological burden of chronic disease management and depression,may contribute to ED.The comorbidity of ED in T1 DM patients is associated with poorer glycemic control and consequently higher rates of diabetes complications.Early recognition and adequate treatment of ED in T1 DM is essential.     

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.     

Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.