Diabetic cardiomyopathy: Pathophysiology,diagnostic evaluation and management

Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population. Diabetes-related heart disease occurs in the form of coronary artery disease (CAD), cardiac autonomic neuropathy or diabetic cardiomyopathy (DbCM). The prevalence of cardiac failure is high in the diabetic population and DbCM is a common but underestimated cause of heart failure in diabetes. The pathogenesis of diabetic cardiomyopathy is yet to be clearly defined. Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn implicated. The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DbCM. In the early stages of the disease diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction. Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used recently for early detection of DbCM. The management of DbCM involves improvement in lifestyle, control of glucose and lipid abnormalities, and treatment of hypertension and CAD, if present. The role of vasoactive drugs and antioxidants is being explored. This review discusses the pathophysiology, diagnostic evaluation and management options of DbCM.     

Diabetes-induced changes in cardiac voltage-gated ion channels

Diabetes mellitus affects the heart through various mechanisms such as microvascular defects, metabolic abnormalities, autonomic dysfunction and incompatible immune response. Furthermore, it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM) in the absence of coronary artery disease. As DCM progresses it causes electrical remodeling of the heart, left ventricular dysfunction and heart failure. Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients. In recent studies, significant changes in repolarizing K~+ currents, Na~+ currents and L-type Ca~(2+) currents along with impaired Ca~(2+) homeostasis and defective contractile function have been identified in the diabetic heart. In addition, insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients. There are many diagnostic tools and management options for DCM, but it is difficult to detect its development and to effectively prevent its progress. In this review, diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.     

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.     

Cardiovascular autonomic neuropathy in diabetes: Pathophysiology,clinical assessment and implications

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.     

Diabetes and cardiac autonomic neuropathy: Clinical manifestations,cardiovascular consequences,diagnosis and treatment

Cardiac autonomic neuropathy (CAN) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. CAN is caused by the impairment of the autonomic nerve fibers regulating heart rate, cardiac output, myocardial contractility, cardiac electrophysiology and blood vessel constriction and dilatation. It causes a wide range of cardiac disorders, including resting tachycardia, arrhythmias, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction and increased rate of mortality after myocardial infarction. Etiological factors associated with autonomic neuropathy include insufficient glycemic control, a longer period since the onset of diabetes, increased age, female sex and greater body mass index. The most commonly used methods for the diagnosis of CAN are based upon the assessment of heart rate variability (the physiological variation in the time interval between heartbeats), as it is one of the first findings in both clinically asymptomatic and symptomatic patients. Clinical symptoms associated with CAN generally occur late in the disease process and include early fatigue and exhaustion during exercise, orthostatic hypotension, dizziness, presyncope and syncope. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Medical therapies, including aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, prostoglandin analogs and alpha-lipoic acid, have been found to be effective in randomized controlled trials. The following article includes the epidemiology, clinical findings and cardiovascular consequences, diagnosis, and approaches to prevention and treatment of CAN.     

Cardiac autonomic neuropathy in patients with diabetes mellitus简

Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.     

Cardiac autonomic neuropathy in patients with diabetes mellitus

Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.     

Role of novel biomarkers in diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM) is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension. As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate, various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM, with little success so far. Hence, we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM. Among the array of biomarkers we thoroughly analyzed, long noncoding ribonucleic acids, soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection, as their plasma/serum levels accurately correlate with the early stages of DCM. The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients. The purpose of the screening test would be to direct affected patients to more specific confirmation tests. This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.     

Molecular and biochemical trajectories from diabetes to Alzheimer’s disease: A critical appraisal

Diabetes mellitus (DM), a metabolic disorder is a major orchestra influencing brain and behavioral responses via direct or indirect mechanisms. Many lines of evidence suggest that diabetic patients apparently face severe brain complications, but the story is far from being fully understood. Type 2 diabetes, an ever increasing epidemic and its chronic brain complications are implicated in the development of Alzheimer’s disease (AD). Evidences from clinical and experimental studies suggest that insulin draws a clear trajectory from the peripheral system to the central nervous system. This review is a spot light on striking pathological, biochemical, molecular and behavioral commonalities of AD and DM. Incidence of cognitive decline in diabetic patients and diabetic symptoms in AD patients has brought the concept of brain diabetes to attention. Brain diabetes reflects insulin resistant brain state with oxidative stress, cognitive impairment, activation of various inflammatory cascade and mitochondrial vulnerability as a shared footprint of AD and DM. It has become extremely important for the investigators to understand the patho-physiology of brain complications in diabetes and put intensive pursuits for therapeutic interventions. Although, decades of research have yielded a range of molecules with potential beneficial effects, but they are yet to meet the expectations.     

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.     

Differences in heart rate variability parameters during the post-dialytic period in type II diabetic and non-diabetic ESRD patients.

BACKGROUND: Heart rate variability parameters were evaluated in 10 healthy subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD) patients (11 non-diabetic and nine type II diabetic) undergoing chronic haemodialysis. The study was divided in two phases. METHODS: In the first phase all subjects underwent electrocardiograph (ECG) recording under baseline conditions. In the second phase only ESRD patients underwent haemodialysis and ECG recording. On the day of dialysis and ECG recording the ECG recording was started 1 h before the haemodialysis session (pre-dialytic period), and continued throughout the dialysis (dialytic period), until the morning after (post-dialytic period). RESULTS: Compared with ESRD patients, non-ESRD patients showed the lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic period (P < 0.01). During the dialytic period in comparison with the pre-dialytic one, a further increase in cardiac sympathetic activity was observed in both diabetic and non-diabetic ESRD patients (P < 0.001). However, in the post-dialysis period the cardiac autonomic nervous system activity remained at the pre-dialytic condition in the diabetic group. In contrast, in the non-diabetic group the cardiac autonomic balance shifted towards a parasympathetic prevalence in the post-dialytic period (P < 0.01). In addition, a significant correlation was found between changes in heart rate variability and changes in plasma urea concentration in the non-diabetic group only (r = 0.65; P < 0.03). CONCLUSIONS: Non-insulin-dependent diabetic uraemic patients undergoing a chronic haemodialysis programme have a severe impairment of heart rate variability. This is probably due to autonomic neuropathy related to the effects of both diabetes and chronic uraemic conditions. In non-diabetic haemodialysis patients uraemia causes similar but reversible changes in heart rate variability compared with the changes caused by diabetes.     

Risks of rapid decline renal function in patients with type 2 diabetes

Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general, it is defined by the decrease of estimated glomerular filtration rate (eGFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained decline in eGFR of > 5 mL/min per 1.73 m² per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection.     

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.     

Ischaemia imaging in type 2 diabetic kidney transplant candidates--is coronary angiography essential?

BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death in type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is a high prevalence of silent CAD in these patients. Controversy exists regarding the role of dobutamine stress echocardiography (DSE) in detection of CAD. Our purpose was to compare DSE with coronary angiography (CA) for the detection of CAD in type 2 diabetic patients undergoing evaluation for renal transplantation. METHODS: Forty (36 male, four female) type 2 diabetic patients with end-stage renal disease (ESRD) were subjected to DSE followed by CA as a part of their pre-renal transplant evaluation. The ability of DSE to predict 70% stenosis in one or more coronary arteries as determined by CA was evaluated. Mean age of the patients was 49.2 +/- 5 years (range 39-60 years). RESULTS: DSE was positive in 10 (25%) patients, while 19 patients (48%) had a more than 70% lesion in at least one epicardial vessel on CA (six patients had single vessel, three had double vessel and 10 had triple vessel disease). The sensitivity and specificity in identifying CAD was 47.3 and 95.2%, respectively, while positive predictive value and negative predictive value was 90% and 66%. Accuracy of DSE was 72.5%. All four patients with diffuse diabetic coronary artery disease had negative DSE. CONCLUSION: DSE is a poor predictor of coronary artery disease in type 2 DM patients being evaluated for renal transplantation. CA should be included in evaluation of type 2 diabetic patients who are renal transplant candidates.     

Diabetes and cardiovascular disease: Epidemiology,biological mechanisms,treatment recommendations and future research

The incidence of diabetes mellitus(DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease(CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular(CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions.     

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.     

2型糖尿病合并肾脏损害的病理与临床分析

目的 分析2型糖尿病患者出现肾脏病变时病理诊断与临床表现的关系.探讨肾活检在2型糖尿病伴有肾脏病变诊断的意义.方法 分析52例尿检异常和（或）Scr升高的2型糖尿病患者的临床特征和病理改变特点.结果 52例2型糖尿病患者经肾活检,32例确诊为糖尿病肾病（DN）,占61.5%,其中3例为糖尿病肾病合并非糖尿病性肾脏疾病（NDRD）;余20例为非糖尿病性肾脏疾病,占38.5%.肾活检前后诊断符合率46.15%,误诊率19.23%.两组间除BUN、Scr、糖尿病病程和是否伴有糖尿病性视网膜病变有显著差异外,其他临床表现和实验室检查的差异均无统计学意义.结论 2型糖尿病伴肾脏病变时相当部分是非糖尿病性肾脏病变,单纯依靠临床资料常难以鉴别,肾活检对明确糖尿病伴肾病变的性质具有重要的意义.     

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.     

糖尿病慢性下肢静脉病变特点及其风险因素分析

目的 观察糖尿病静脉病变患者的临床特点,探讨与慢性静脉疾病病情加重相关的危险因素。方法 收集2018年9月至2019年1月于中山大学孙逸仙纪念医院血管外科住院的合并糖尿病（DM组）或非合并糖尿病（NC组）的慢性下肢静脉疾病患者共44例,对比两组患者的静脉病变临床表现。按静脉病变程度将患者分为4组,对比各组间基线资料,采用有序多分类Logistic回归分析与慢性下肢静脉疾病加重相关的危险因素。结果 糖尿病患者的静脉病变较非糖尿病患者更为严重;合并糖尿病和高水平肌酸激酶同工酶（CM-KB）是慢性静脉病变加重的风险因素。结论 糖尿病患者的慢性静脉疾病较非糖尿病患者更严重;合并糖尿病、高水平CK-MB可以作为慢性静脉疾病加重高风险的评估因素。     

Diabetic cardiomyopathy: Pathophysiology,theories and evidence to date

The prevalence of type 2 diabetes(T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.