SD：Symposium-Diabetes (1-6

SD1-1 FRAILTY AND SARCOPENIA IN OLDER ADULTS WITH DIABETES

LIANG-KUNG CHEN

Aging and Health Research Center, National Yang Ming University Center for Geriatrics and Gerontology, Taipei Veterans General Hospital

Diabetes mellitus is a prevalent condition of older adults, and the management may differ greatly from younger counterpart. The epidemiological study clearly showed that disability and dementia may be strong predictors than multimorbidity for adverse health outcomes in older people, which highlights the importance of prevention for disability and dementia. In particular, frailty and sarcopenia are two major foci to prevent disability. Sarcopenia, so-defined as the age-related loss of muscle mass plus loss of muscle strength and/ or loss of physical performance, is a newly defined disease entity. Age-related changes in body compostion is featured by the loss of bone mass, muscle mass and increase of fat mass. Nevertheless, sarcopenia is never a normal aging process, which is associated with mortality and morbidity.

Diabetes, frailty and sarcopenia are highly interrelated conditions in older populations. Chronic inflammation and altered energy metabolism of cardiometabolic disease may accelerate muscle wasting. On the other hand, sarcopenia is also associated with higher risk of diabetes due to the loss of mitochondria.

In modern clinical practice, adding consideration of disability and dementia into diabetes care is of critical importance. On the other hand, more attentions should be paid to diabetes patients with frailty and/or sarcopenia.

SD1-2 COGNITIVE IMPAIRMENT AND DIABETES: RECIPROCAL RELATIONS AND CLINICAL IMPLICATIONS

PEI-NING WANG

Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan

There is evidence of the association between diabetes, cognitive decline and dementia. The duration of diabetes, glycated hemoglobin levels and glycemic fluctuations were associated with cognitive decline and dementia. Furthermore, diabetes not only increases the risk of vascular dementia but also Alzheimer’s disease (AD). AD is the most common type of dementia that is characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD.

Correspondingly, hypoglycemia was significantly related to increased risk of developing cognitive decline and dementia. Acute or severe hypoglycemia, i.e., depriving the brain of glucose, is associated with neuronal damage in the hippocampus and cerebral cortex. Hypoglycemia is a frequent clinical situation in the strict management of diabetes and is well known as an important factor that directly affects the risk of dementia and cognitive impairment. In patients aged ≥65 years with type 2 diabetes, higher glucose variability and lower average glucose levels are noted and indicate a greater hypoglycemia risk. Elderly patients with T2DM combined with AD may benefit more from the moderate control of blood glucose and a proper increase of the target value.

There are some studies and clinical trials showed the types of anti-diabetic treatment may have influence in the protection of cognition decline in patients with type 2 diabetes. However, the recent Cochrane review found no good evidence that any specific treatment or treatment strategy for Type 2 diabetes can prevent or delay cognitive impairment.

SD2-1 INTRODUCTION OF DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE- 2018

HUNG-YUAN LI

Department of Internal Medicine, National Taiwan University Hospital

Based on the findings of various reports, it is estimated that there were 1.73-2.20 million people with treated diabetes in Taiwan in 2014-2015. There is no change in the diagnostic criteria for diabetes, which can be made by fasting plasma glucose, 2-hour plasma glucose during a 75g oral glucose tolerance test and hemoglobin A1c. Physicians can differentiate type 1 and type 2 diabetes by clinical presentation, plasma c-peptide concentration, the presence of auto-antibodies and treatment response. Gestational diabetes mellitus can be diagnosed by “one-step” method using 75g oral glucose tolerance test or by “two-step” method using 50g glucose challenge test followed by 100g oral glucose tolerance test. There are 3 different screening methods suggested by the guideline. One is based on the service by the National Health Insurance in Taiwan, one is based on Taiwan Diabetes Risk Scores, and the other one is based on risk factors of diabetes. For these high-risk groups, results from fasting plasma glucose and hemoglobin A1c can be used to determine the need of an oral glucose tolerance test.

Generally, the treatment goals for adults with diabetes are fasting plasma glucose 80-130 mg/dL, post-prandial plasma glucose 80-160 mg/dL and hemoglobin A1c < 7%. However, these goals should be individualized. For the older adults, less stringent treatment goals can be set according to their health status. For children and adolescents with type 1 diabetes, the general treatment goals are fasting plasma glucose 90-130 mg/dL, plasma glucose before sleep 90-150 mg/dL and hemoglobin A1c < 7.5%, with individualized considerations. For women with gestational diabetes, the treatment goals are fasting plasma glucose < 95 mg/dL, 1-hour post-prandial plasma glucose < 140 mg/dL, 2-hour postprandial plasma glucose < 120 mg/dL and glycated albumin < 15.8%.

The guideline recommend a treatment algorithm for people with type 2 diabetes. Physicians should consider patient’s current glycemic control, risk of hypoglycemia, body weight, risk of cardiovascular diseases and adverse effect, in order to determine the appropriate pharmacological therapy for the patient. Besides, regular monitoring is recommended, which includes plasma glucose, hemoglobin A1c, lipid profile, renal function, the presence of diabetic complications including retinopathy, nephropathy, neuropathy and diabetic foot diseases, oral examinations, and screening for cancers. For diabetic inpatients, the general glycemic control is plasma glucose 140-180 mg/dL. Individual consideration is needed for a more or less stringent goal.

SD2-2 2018 DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE--THE DIAGNOSIS AND TREATMENT FOR DIABETES IN PREGNANCY

CHUN-HENG KUO

Division of Endocrine & Metabolism, New Taipei City Hospital, New Taipei City, Taiwan, ROC

For many years, gestational diabetes mellitus (GDM) is diagnosed by two-step strategy, using a nonfasting 1-hour 50g glucose load test (GLT) screen, followed by a 3-hour 100g oral glucose tolerance test (OGTT) for those who screen positive. In 2008, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study found that plasma glucose values during a 2-hour 75g OGTT can predict adverse pregnancy outcomes, including increased frequency of birth weight, cord serum C-peptide levels, and infant adiposity > 90th percentile. This is the first outcome-based large scale study to provide evidence-based clinical judgment to diagnose GDM. Based on the findings, the International Association of the Diabetes and Pregnancy Study Group (IADPSG) proposed new diagnostic criteria using one-step approach by a 2-hour 75g OGTT to screen all pregnant women, which was adopted by many organizations including the World Health Organization (WHO) and the American Diabetes Association (ADA).

In 2018 DAROC guidelines, we adopted ADA diagnostic criteria for GDM, which can be accomplished with either one-step or two-step approach. Besides, screening for preexisting diabetes mellitus (PDM) was also recommended for all pregnant women at the first prenatal visit. By definition, diabetes in pregnancy (DIP) can be classified as PDM or GDM.

Since treatment would reduce the adverse perinatal outcomes, it should be initiated soon after the diagnosis of DIP. All pregnant women diagnosed with DIP were recommended to receive nutrition and exercise counseling. Most women diagnosed with GDM would achieve glycemic targets by lifestyle modification alone. For PDM women or GDM women who cannot achieve glycemic goals, pharmacologic therapies should be given. Insulin is the first-line regimen recommended for treatment of both PDM and GDM. Metformin and glyburide can be used for the treatment of GDM although the long-term safety trials for both medications are not available yet.

SD2-3 THE EVOLUTION OF DIABETES MANAGEMENT (SGLT2I + GLP-1 RA + TOUJEO/DEGLUDEC + CGM)

CHIH-HSUN CHU

Division of Endocrinology and Metabolism, Department of Medicine, Kaohsiung Veterans General Hospital, Taiwan

Antidiabetic medications include oral antidiabetic agents and injectable agents (insulin and GLP1 RA). Metformin is always the first line medication. In dual therapy the medications with evidences to reduce cardiovascular events or mortality should be considered in patients with atherosclerotic cardiovascular disease. The antidiabetic medications proved to have cardiovascular benefit include SGLT2i and GLP-1 RA.

The novel long-acting basal insulin analogues (Toujeo/degludec) have evidence to reduce hypoglycemia. Though high costs of analog insulin, they may be a practical option for some patients, and clinicians should be familiar with its use.

The continuous Glucose Monitoring (CGM) is a device that provides continuous insight into glucose levels throughout the day and night. It can help to detect the unaware hypoglycemia or hyperglycemia and to provide additional information with the diabetes management.

SD3-1 ORAL ANTIHYPERGLYCEMIC THERAPY IN PATIENTS WITH TYPE 2 AND ASCVD – EVIDENCE AND CLINICAL PRACTICE RECOMMENDATIONS

JULIANA CHAN

Chair Professor of Medicine and Therapeutics and Director, Hong Kong Institute of Diabetes and Obesity and Director, Clinical Research Management Office, The Chinese University of Hong Kong, Prince of Wales Hospital.

The frequent co-existence of obesity, hypertension and dyslipidemia have put people with type 2 diabetes at high risk of cardiovascular-renal disease and premature death. While the use of statins and renin-angiotensin system inhibitors have improved their clinical outcomes, obesity and hyperglycemia contributed to their residual risk for these life threatening events. The new drug classes including incretin therapy and sodium glucose transporter inhibitors (SGLT2i) have provided opportunities to reduce hyperglycemia with low risk of hypoglycemia and weight neutral or reducing effects. The effects of reducing cardiovascular events, renal failure, heart failure and all-cause death with SGLT2i in EMPA-REG and to some extent CANVAS are particularly noteworthy. These trial data were also supported by real-world evidence in more diverse populationsmaking this class of drug an important armamentariumin these high risk patients with suboptimal control. The rapid onset of clinical benefits of SGLT2i raised important questions regarding the pathogenetic roles of abnormal water and sodium homeostasis and haemodilution with ongoing studies in patients with heart failure and chronic kidney disease. Although the neutral effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiovascular outcomes were disappointing, its excellent tolerability in patients with chronic kidney disease and low blood glucose variability with sustained glycemic durability might be translated to long term benefits. In a meta-analysis, glycemic burden was the main determinant in explaining the cardiovascular benefits in these blood glucose lowering outcome trials and that if glycemic control could be sustained, long term benefits as reported in the UKPDS would be expected. Despite these encouraging results, the challenge lies in closing the huge treatment gaps in this growing population of people with diabetes, especially in young people who face long disease duration. To this end, system change is needed to create a practicing environment which enablesthe care team to systematically phenotype these individuals, reduce clinical inertia and treatment non-adherence in order to reduce these preventable hospitalizations, morbidity and premature death.

SD3-2 THERAPEUTIC ADVANCES WITHNEW INSULIN ANALOGUE AND GLP-1RA BASED ON RECENT CVOT RESULTS

MASATO ODAWARA

Affiliation,The Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University

Diabetes, a global emergency, is a major risk factor for cardiovascular diseases (CVD). Up to 41% of diabetic patients have a history of CVD and individuals with diabetes are 2 – 4 times more likely to die from CVD than people without diabetes.

Severe hypoglycemia should be avoided based on learnings from the ACCORD and VADT. The sub-analysis of DEVOTE trial confirming cardiovascular safety of insulin degludec vs glargine, has recently shown that higher day-to-day fasting glycemic variability is associated with increased risk of severe hypoglycemia and all-cause mortality. In addition, some GLP-1 receptor agonists (GLP1RA) have been shown to reduce cardiovascular risk in CVOTs, leading to be recommended for type 2 diabetic patients with atherosclerotic cardiovascular diseases (ASCVD) in Standards of Medical Care in Diabetes.

In this symposium, I would like to discuss therapeutic advances of new insulin analogues and GLP-1RAs for diabetic patients with ASCVD based on recent evidence.

SD4-1 PROTECTIVE ROLE OF THYROID HORMONE IN LIVER CARCINOGENESIS

KWANG-HUEI LIN

Department of Biochemistry, Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan

Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showtwo models to elucidate the protect role TH during hepatocarcinogenesis. Depletion of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy related 7)via adeno-associated virus(AAV)vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase),which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protectshepatocytes fromDEN-induced hepatotoxicity or carcinogenesis.

Infection by hepatitis B virus (HBV) accounts for 50~80% of HCC development worldwide, in which the HBV encoded X protein (HBx) plays critical role in the induction of carcinogenesis. Several studies have shown that TH suppresses HCC development and protects hepatocytes from HBx induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of ROS inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted mitochondria simultaneously, consequently leading to suppression of HBxpromoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger

selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicates thatTH/PINK1/Parkin pathway plays a critical role in protecting hepatocytes from HBxinduced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of thyroid hormone facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T3 constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.

SD4-2 ROLE OF ADIPOCYTE HYPERTROPHY AND HYPOXIA IN THE DEVELOPMENT OF ADIPOSE TISSUE INFLAMMATION AND INSULIN RESISTANCE – THE INVOLVEMENT OF COX-2 ACTIVATION

PO-SHIUAN HSIEH

Institute of Preventive Medicine, National Defense Medical Center, Taiwan, ROC

Adipose tissue inflammation has been suggested to play a central role in the pathogenesis of many obesity-associated complications including insulin resistance and type 2 diabetes. Adipocyte hypertrophy and hypoxia especially in morbid obesity are the important sources for the development of adipose tissue inflammation. This inflammation is mediated by producing a large number of cytokines and chemokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and regulated upon activation, normal T-cell expressed and secreted (RANTES). Of note, these cytokines and chemokines produced by adipocytes during hypertrophy and hypoxia are crucially involved in the initiation and development of obesity-associated inflammatory response in adipose tissue. The capacity of constitutive and regulated release of immune mediators from adipocytes demonstrates a causal link between the biology of adipocytes and immune cells, such as macrophages and T cells. Moreover, the synergistic effect of hypertrophic, hypoxia adipocytes, and adipose tissue immune cells has also been implicated in the development of obesity-induced insulin resistance.

Our study provides the supportive evidence to demonstrate the important role of COX2 activation in development of adipocyte hypertrophy and hypoxia in the pathogenesis of obesity associated adipose tissue (AT) inflammation and insulin resistance.

SD5-1 DIABETIC NEUROPATHY: PERCEPTION BEYOND THE SEAM OF THE PERIPHERY

SOLOMON TESFAYE

Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield.

Diabetic peripheral neuropathy (DPN) is a common, debilitating and distressing complication of diabetes. Most patients develop painless, insensate distal nerve damage which increases the risk of foot ulceration and subsequent amputation. Amputation is not only devastating in its impact on the person with diabetes and their family, leading to loss of independence and livelihood; it is also very expensive in material terms and results in only 50% surviving for two years. Around a quarter of all diabetic patients also develop a chronic painful condition mainly affecting the legs which can result in considerable disability and suffering. Many such patients with painful DPN have depression, anxiety, fear and stress, and do not sleep well. There is thus an urgent need to detect DPN early by using objective, validated point-of-care devices as clinical exam or the use of the 10 gram monofilament is not reliable. Early detection will lead to an earlier intervention to reduce risk factors for the development of DPN.

There has also been emerging evidence that DPN may not be as its name suggest, and may involve the central nervous system. We have reported the involvement of the spinal cord in DPN on MRI. More recently we have reported the involvement of the brain in DPN by demonstrating: 1) thalamic neuronal dysfunction using MR Spectroscopy, 2) increased thalamic vascularity in painful DPN on MR perfusion imaging and disruption of the resting state network connectivity on functional MRI. If we are able to develop non-invasive, objective biomarkers of painful DPN this would be a great advance as it would serve as a target for the development of new drugs for this distressing condition. The symptomatic management of painful DPN continues to pose considerable challenge to clinicians as less than 50% of patients respond to current drugs. Innovative, head-to-head and combination trials of new and existing drugs are required. We have obtained $4.8 m funding from the UK NIHR to conduct such a trial. Finally, there is early evidence that a patient’s pain phenotype may determine response to treatment although further studies are required.

SD5-2 GLYCEMIC CONTROL FOR PATIENTS WITH CEREBROVASCULAR DISEASE

JIANN-SHING JENG

Stroke Center & Department of Neurology, National Taiwan University Hospital

Subjects with diabetes mellitus (DM) are at two-to six-fold increased risk of stroke, with the higher risk in young patients or type 1 DM. Data from Taiwan’s National Health Insurance, the incidence of stroke in DM and non-DM was 10.1 and 4.5 per 1000 person-year, respectively, and the hazard ratio was 1.75 (1.64–1.86).Due to yearly increase in DM prevalence in Taiwan, the contribution of DM to stroke is expected to increase gradually. By the Taiwan Stroke Registry during 200608 in 30599 stroke patients, the prevalence of DM in ischemic stroke was 45% and in intracerebral hemorrhage was 37%. Besides, acute stroke patients with DM often have greater stroke severity, more unfavorable functional outcome and mortality, and higher stroke recurrence than those without DM.

Admission hyperglycemia is a well-established independent predictor of neurological worsening and poor outcome following stroke.Post-strokehyperglycemia has been associated with increased cytotoxic edema, blood-brain-barrier disruption, hemorrhagic transformation, lower likelihood of recanalization and deteriorating neurological state. Besides, hyperglycemia may decrease the efficacy and increase the hemorrhagic transformation in acute ischemic stroke patients receiving reperfusion therapy. Thus, hyperglycemia in acute stroke may lead to higher stroke severity, more stroke in evolution, poorer functional outcome. While correcting hyperglycemia, great care should be taken to avoid hypoglycemia, and subsequently aggressive insulin administration treatment is not suggested.For most patients, the goal of regular treatment is euglycemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. Newer glucose-lowering agents, including thiazolidinediones, GLT-1 agonists and SGLT-2 inhibitors have shown decrease in the risk of cardiovascular events in recent randomized, placebo controlled trials. Of these, semaglutide showed reduced the risk of ischemic stroke. Except for glucose lowering effect, the cardiovascular benefit might be due to body weight and blood pressure reduction which are also important for stroke prevention.

SD6-1 GROWING CHALLENGE OF DIABETIC NEPHROPATHY

DAISUKE KOYA

Division of Diabetology & Endocrinology, Kanazawa Medical University

Diabetic nephropathy is not only a leading cause of end stage renal disease (ESRD), but also associated with higher risk of ASCVD. Tight blood glucose and bold pressure control with RAS inhibitors have shown to reduce the development and progression of diabetic nephropathy. However, renal hard events defined by doubling of sCr and/or ESRD remain unsolved yet. Here, we talk about the promising effects of DPP-4 inhibitor on the progression of diabetic nephropathy as well as the crucial effects of SGLT2 inhibitors on renal hard endpoints. Three randomized clinical trials with DPP-4 inhibitors failed to show the beneficial effects on 3-point MACE. However, treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial saxagliptin in the SAVOR-TIMI 53 Trial. We have also reported that the switching other DDP-4 inhibitors toanagliptin was associated with improvement of albuminuria as well as tubular injury defined by urinary L-FABP in type 2 diabetic patients with albuminuria>30mg/gCrindependent on glucose control. Indeed, we have revealed the underlying mechanism of DPP-4 inhibitor by which resolved diabetes-induced renal fibrosis possibly through the inhibition of endothelial-mesenchymal transition in type 1 diabetic mice.

Surprisingly, SGLT2 inhibitors such as empagliflozin and canagliflozin has shown to prevent the development of ESRD defined by sustained 40% loss of eGFR and/or doubling of sCr, renal replacement therapy, and renal death in EMPA-REG Outcome and CANVAS program in addition to reduction of 3-point MACE, CV death, and total mortality although type 2 diabetic patients with CKD defined by albuminuria and eGFR< 60ml/min/1.73 m2 were about 30% of all precipitants. Other SGLT2 inhibitors have also demonstrated the renoprotective effects in type 2 diabetic patients. Mechanistically, SGLT2 inhibitors reverse diabetes-induced hemodynamic alteration by normalization of tubuloglomerular feedbackand also protect against higher glucose and sodium-dependent tubular injuries.

SD6-2 GLUCOSE CONTROL IN DIABETIC PATIENTS WITH MODERATE AND ADVANCED KIDNEY DISEASE

林俊良

嘉義長庚醫院內科教授

Chronic kidney disease (CKD) is associated with insulin resistance and, in advanced CKD, decreased insulin degradation. The latter can lead to a marked decrease in insulin requirement or even the cessation of insulin therapy in patients with type 2 diabetes. Both of these abnormalities are at least partially reversed with the institution of dialysis. Because of the uncertainty in predicting insulin requirements, careful individualized therapy is essential among patients who have advanced CKD or are initiating dialysis. This lecture will review glycemic targets, methods of monitoring glycemic control, and suggested treatment regimens for patients on CKD, hemodialysis and peritoneal dialysis. The treatment of nondialysis CKD and dialysis patients with diabetes involves both nonpharmacologic and pharmacologic therapies. The nonpharmacologic therapies include dietary modification, exercise, and weight reduction. Pharmacologic therapies include insulin and oral agents. Our pharmacologic approach varies depending upon whether patients have predialysis CKD or are on dialysis. For most hemodialysis patients with type 2 diabetes, we suggest initial treatment with insulin, rather than oral agents Some clinicians prefer to use oral agents rather than insulin, especially among patients who have already achieved acceptable glycemic control on these agents. If an oral agent is used, the preferred agents are glipizide or repaglinide. For peritoneal dialysis patients with type 2 diabetes who were already on an oral agent with good glycemic control prior to starting dialysis and for patients who develop diabetes after starting dialysis, we suggest using an oral agent, rather than insulin. For PD patients, we suggest the use of subcutaneous, rather than intraperitoneal, insulin. Severe hyperglycemia may be observed among dialysis patients with diabetes. Instead of fluid replacement, management is principally dependent upon the administration of low doses of intravenous insulin.