Our understanding of genetic mechanisms that define complex traits has been hindered by the difficulty of obtaining comprehensive omics datasets across a broad range of biological “layers”. Complete data on the genome of individuals can be readily obtained, but the full complexity of the transcriptome, proteome, metabolome, and phenome have remained largely out of reach. This is, however, beginning to change, with the development of robust multi-layered omics strategies that are pioneered in model organisms. We here profiled the healthspan and lifespan in > 80 cohorts of the BXD mouse genetic reference population. Large variability was observed across all omics layers; to understand how these differences stem from genetic variance, we exploited a multilayered set of molecular phenotypes―genomics, transcriptomics, proteomics, and metabolomics. With this multi-omics strategy, large networks of proteins could be analyzed and causal variants identified in proteins involved in determination of lifespan (e.g. Mrps5, Jmjd3), glucose homeostasis (e.g. Dhtkd1), hypertension (Ubp1) and in mitochondrial supercomplex formation (Cox7a2l ). These new candidates were then validated using cross-species genetic strategies in C.elegans, mouse, and human. Our large-scope multi-omics measurements in mouse populations combined with cross-species validation hence provided us with robust conserved and mechanistically defined pathways that underpin complex traits involved in metabolism and aging.

The prevalence of diabetes or metabolic syndrome (MetS) has steadily increased in Korea and obesity is one of the most important risk factors for them. The prevalence of MetS in Korea increased rapidly from 24.9% in 1998 to 31.3% in 2007 and so did the prevalences of diabetes and obesity. MetS was associated with an increased risk of cardiovascular diseases (CVDs), and in particular was associated with the risk of coronary heart disease (CHD) in men and stroke in women. Diverse risk factors for either diabetes or metabolic syndrome have been reported, such as age, dietary habits, physical fitness, sleep deprivation, and decreased heart rate recovery (HRR). It has also been reported that the serum calcium concentration is positively correlated with glucose level. In addition, serum bilirubin has been consistently shown to be negatively correlated with the cardiovascular diseases (CVDs) as well as with CVD-related diseases and risk factors such as arterial hypertension, diabetes, MetS, and obesity. We analyzed data from the Korean Health and Genome Study to examine the association of serum total bilirubin (TB) and corrected calcium levels with the risk of DM development. DM incidence increased across baseline TB and calcium tertile categories. Hazard ratio (HR) for developing DM was higher in the highest tertiles compared with the lowest after adjusting for confounding variables. These results suggest that there could be multiple, diverse risk factors for diabetes and metabolic syndrome, which should be considered in the development of prevention strategies.

Pyruvate dehydrogenase complex (PDC) is a key enzyme to control metabolic flux during the fed-fast cycle. Adequate regulation of PDC is very important not only in the rapid selection of fatty acid and glucose metabolism and also in adequate selection of metabolic fate for glycolysis and oxidative phosphorylation. The main mechanism of insulin resistance followed by dietary fat-induced obesity is closely associated with mitochondrial dysfunction and endoplasmic reticulum (ER) stress. In this presentation, we want to show the role of pyruvate dehydrogenases kinase(PDK) involved in dietary fat-induced insulin resistance, used Wild-type (WT) mice and several different models of global pyruvate dehydrogenase kinase(PDK) knockout mice such as PDK2 knockout mice, PDK4 knock mice on fed low fat (LFD) or high fat (HFD) diets.

Care of the older person with diabetes can't be restricted to the management of hyperglycemia, associated risk factors, and specific diabetic complications. An integrated approach should include also the assessment and management of gerontological problems.
Gerontology is composed of 3 fields such as gerontological biology, gerontological sociology, and geriatric medicine. What is the practical way to integrate the gerontological features of older person with diabetes to the management of the older person with diabetes? I selected one topic from each field of gerontology, vascular aging from biology, health literacy from sociology, and geriatric syndrome from geriatric medicine respectively.
Fluctuating glucose levels increased proliferation and migration of OLETF rat vascular smooth muscle cells (VSMCs) via MAPK (ERK1/2), BMK1, PI3K, and NF-κB pathways. These effects were inhibited by the antioxidant rutin.
Only 23.8% of elderly diabetic patients had appropriate health literacy. Older persons with diabetes were heterogenous in social aspects including health literacy.
Both his diabetes mellitus and his aging interact toward the direction of the increased incidence of the geriatric syndromes. Education is a common element of both diabetes control and geriatric syndrome care. But it has been perceived that conventional education (CE) programs for diabetics are not as effective for the older. We designed a geriatrically reinforced education (GRE) for application in older diabetics with geriatric syndromes. We observed that the application of GRE made glucose control and the status of geriatric syndromes get better in older adults with diabetes.
In summary, in terms of the integrating care of coexisting diabetes and geriatric problems, geriatrically reinforced education (GRE) may be a beneficial tool on the management of older adults with diabetes.

Inhibition of renal glucose reabsorption by the inhibition of the Sodium Glucose Transporter 2 (SGLT2) has emerged as not only a practical way to lower glucose levels in patients with type 2 diabetes without increasing the risk of hypoglycaemia or weight gain, but also with the clear potential for vasculoprotective effects that are independent to the achieved glucose control. The strong expectation surrounding drugs of this class has led to a rapid expansion of their use. However, such exciting data should be tempered by the potential for adverse effects, as the first priority in our patients must be to minimise the potential for harm. It is clear that complete deficiency of SGLT2 in humans is not dangerous, and leads to a condition known as benign familial glycosuria. Consequently, subtotal blockade of SGLT2 that occurs during pharmacological inhibition is often considered equally benign. However, in the setting of diabetes, SGLT2 inhibition increases urine output proportional to glycosuria, resulting in troublesome polyuria and nocturia in some patients, especially those with bladder/pelvic floor/prostate dysfunction. SGLT2 inhibition increases the frequency of genital mycotic infections in both men and women, although both are readily treatable and rarely severe or recurrent. Curiously, urinary tract infects are not increased by SGLT2 inhibitors, possibly as increased urine flow/frequent bladder emptying offsets the effect of glycosuria. Recent data has also emerged that SGLT2 inhibition increases ketogenesis, and in some selected settings may be associated with ketoacidosis. For the most part, each of these adverse effects can be mitigated by judicious prescribing and treatment planning.

Vascular complications are the most important cause of morbidity and mortality in patients with diabetes. Macrovascular complications consist of coronary artery disease (CAD) and cerebrovascular disease, while microvascular complications embrace nephropathy, neuropathy, and retinopathy. Recently, incretin-based therapy, such as dipeptidyl peptidase IV inhibitors (DPP4I) or glucagon-like peptide-1 (GLP-1) receptor agonists, has drawn attention as a potential therapeutic option for the prevention of cardiovascular and renal complications in patients with type 2 diabetes. Previous studies have shown that incretin-based therapy can reduce oxidative stress, inflammation, glomerulosclerosis, and fibrosis in kidney as well as albuminuria. Furthermore, accumulating evidence demonstrates the direct and indirect actions of incretin-based therapy on the cardiovascular system. Randomized controlled clinical trials are under way to investigate the impact of incretin-based therapy on cardiovascular and renal outcomes in patients with type 2 diabetes. The present talk will summarize the pathophysiological mechanisms and therapeutic interventions of incretin-based treatment in patients with type 2 diabetes.

The gastrointestinal hormone glucagon-like peptide-1 (GLP-1) lowers postprandial glucose concentrations by regulating pancreatic islet-cell function, with stimulation of glucose-dependent insulin and suppression of glucagon secretion. In addition to endocrine pancreatic effects, mounting evidence suggest that several gastrointestinal actions of GLP-1 are at least as important for glucose lowering. GLP-1 reduces gastric emptying rate and small bowel motility, thereby delaying glucose absorption and decreasing postprandial glucose excursion.
Currently available GLP-1 receptor agonists (GLP-1 RAs) can be categorized as either “short-acting compounds”, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as “long-acting compounds” (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamics profiles.
In this session, I'd like to deal with the similarities and differences between short-acting GLP-1 RAs and long-acting GLR-1 RAs. I hope that this review will help various GLP-1 RAs treatment to be tailored to the needs of each patient with type 2 diabetes.

Relative insulin deficiency with insulin resistance is the main pathogenesis of type 2 diabetes mellitus (T2DM). However, T2DM is a progressive disease, so oral medications may not be enough to control glucose levels, and exogenous insulin is needed in type 2 diabetes eventually.
Insulin is classified into basal and prandial insulin; basal insulins inhibit hepatic glucose production and provide constant level of insulin action throughout the day whereas prandial (mealtime) insulins act rapidly to lower glucose levels following meals. Traditional basal insulin is NPH and it is intermediate-acting (up to 12 hours) with higher risk of hypoglycemia. In contrast, insulin glargine and detemir is relatively long-acting (up to 24 hours) insulin and less hypoglycemia (overall and nocturnal) than NPH. So introduction of insulin glargine and detemir provided an improvement in basal insulin therapy.
Now ultra-long-acting basal insulins like insulin glargine U300 and degludec are available. They have longer half-life, flatter glycemic profiles compared with glargine U100 or detemir as well as NPH. Currently, no specific AACE or ADA recommendations for use of these new basal insulins. Guidelines generally emphasize the value of basal insulin compared with NPH insulin (eg. less hypoglycemia). This lecture will review ultra-long acting basal insulins in detail.

Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. Only < 5% of people with diabetes have this form of the disease. The Diabetes Control and Complications Trial (DCCT) showed definitively that improved glycemic control is associated with significantly decreased rates of microvascular and neuropathic complications in type 1 diabetes.
Proper type 1 diabetes management is composed of a handful of elements: blood glucose control and insulin management, exercise, nutrition and support. The American Diabetes Association recommends using patient age as one consideration in the establishment of glycemic goals, with targets for preprandial, bedtime/overnight, and hemoglobin A1c levels. In 2014, the ADA released a position statement on the diagnosis and management of type 1 diabetes in all age groups. An A1C goal of < 7.5% is recommended across all type 1 pediatric patients, and for many type 1 adults is < 7%. Individualized lower or higher targets may be used based on patient need.
Patients with type 1 diabetes require lifelong insulin therapy. Most people with type 1 diabetes should be treated with multiple-dose insulin injections or continuous subcutaneous insulin infusion. Consider educating individuals with type 1 diabetes on matching prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated activity.
Screening for diabetic complications is an important component of ongoing care. At least once a year, assess urinary albumin and estimated glomerular filtration rate, an initial dilated and comprehensive eye examination and tests for diabetic neuropathy in patients with type 1 diabetes with duration of ≥ 5 years or adult type 1 diabetes.

Type 1 diabetes, which usually happens to the pediatric age group, is one of representative chronic diseases among children. It requires education and management from an experienced professional diabetes team from the moment of diagnosis and asks the patients to self-monitor their blood sugar level for life to prevent complications.
Proper self-management education programs should be provided right after diagnosis and should not be a one-time event but be provided on an ongoing basis.
They can promote the adjustment of patients and their families and play an essential role in their better quality of life.
This lecture will provide an introduction of the various education programs implemented to improve patients' self-management in the clinical field of a hospital and will share the experiences. It will also discuss future-oriented educational programs and their directions.