Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function

BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016).CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.

Impact of Socioeconomic Status on Health Behaviors, Metabolic Control, and Chronic Complications in Type 2 Diabetes Mellitus

BACKGROUND: The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition. METHODS: A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income. RESULTS: Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; P(trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; P(trend)=0.048). In women, lower income was associated with a higher stress level. CONCLUSION: Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population.

Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

BACKGROUND: The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus. METHODS: A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52). RESULTS: During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone. CONCLUSION: Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Emphysematous Gastritis with Concomitant Portal Venous Air and Acute Necrotizing Esophagitis in Type 1 Diabetes with Diabetic Ketoacidosis: A Case Report and Literature Review of a Rare Complication in Diabetes / 임상당뇨병

Emphysematous gastritis is a rare disorder characterized by emphysematous change of the gastric wall due to infection with a gas-forming organism. Acute necrotizing esophagitis is a rare disorder with an unknown pathogenesis. Above two disorders rarely occur together, only three global cases have been reported to date. Such a case has never been reported in Korea, we report a novel case of severe emphysematous gastritis with concomitant portal venous air and acute necrotizing esophagitis in type 1 diabetes presenting with diabetic ketoacidosis. A 24-year-old man known to have type 1 diabetes and pulmonary tuberculosis was brought to the emergency room for epigastric pain with vomiting. His body mass index was 14.7, and the laboratory findings demonstrated leukocytosis and acidosis, as well as elevated serum glucose, ketone, and C-reactive protein levels. Enhanced computed tomography showed portal vein gas and edematous wall thickening without enhancement in the stomach wall, with air density along the stomach and esophageal wall. The patient required surgical intervention of total gastrectomy and cervical esophagostomy followed by esophagocolostomy and esophageal reconstruction. Early radiologic diagnosis and clinical suspicion of this disease and prompt intervention including antibiotics, decompression, and surgery are important for a good prognosis.

Type 1 diabetes genetic susceptibility markers and their functional implications

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic beta-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against beta-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.

Clinical Heterogeneity of Diabetes in Young Korean Patients / 임상당뇨병

Diabetes among young patients in Korea is caused by a complex set of factors. In addition to the typical T1aD and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1b), such as fulminant T1D (FT1D). Although T1a is the major type of childhood diabetes, FT1D exists as a hyper-acute subtype of T1D that affects older children, without causing autoimmunity. They showed a complete loss of beta-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults (LADA) is a form of autoimmune-mediated diabetes, usually diagnosed based on GAD autoantibody positivity. Although many epidemiological surveys of LADA have been conducted in Caucasian and Asian populations, their reported prevalence rates vary due to the use of different diagnostic criteria. In a recent study with a comparable design and valid methodology, the prevalence of LADA using GAD autoantibody positivity as the diagnostic criterion was higher (4.4%) than the previously reported prevalence of 1.7% in a population-based T2D survey. After 36 months of follow-up, only 3 of the 39 patients initially diagnosed with LADA had become insulin-dependent, and they were all positive for multiple autoantibodies (GAD, IA-2 and ZnT8 antibody). This demonstrates that true insulin dependency, which was initially indicated by multiple antibody positivity, has not increased in the Korean population. Therefore, despite etiological heterogeneity, in the clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds without measuring autoantibodies could be a possible method to minimize complications.

Plasma Glucose Regulation and Mortality in Korea: A Pooled Analysis of Three Community-Based Cohort Studies

BACKGROUND: Although diabetes is a well-known risk factor for death, its impact on cancer death is not clearly understood. Furthermore, it remains controversial whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality. We investigated the impact of diabetes or glucose tolerance categories on all cause and cause-specific mortality. METHODS: Mortality analysis was conducted in three population-based cohort studies of 3,801 participants, divided according to fasting plasma glucose (FPG) (normal; stage 1 IFG [5.6< or =FPG<6.1 mmol/L]; stage 2 IFG [6.1< or =FPG<7.0 mmol/L]; diabetes mellitus [DM]-FPG); or 2-hour glucose after 75 g glucose loading (2hPG) (normal; IGT; DM-2hPG), or a combination of FPG and 2hPG criteria. RESULTS: During a median follow-up of 11.0 years, 474 subjects died from all causes. Hazard ratios (HRs) for all cause death were higher in those with diabetes as defined by either FPG or 2hPG criteria than their normal counterparts (HR, 2.2, 95% confidence interval [CI], 1.6 to 2.9 for DM-FPG; HR, 2.0, 95% CI, 1.5 to 2.7 for DM-2hPG). Similarly, diabetes defined by either FPG or 2hPG was associated with cancer death (HR, 2.9, 95% CI, 1.7 to 5.0; and HR, 2.1, 95% CI, 1.2 to 3.9, respectively). Although neither IFG nor IGT conferred higher risk for death, when combining stage 2 IFG and/or IGT, the risk of all cause death was higher than in subjects with normal glucose regulation (HR, 1.3; 95% CI, 1.0 to 1.6). CONCLUSION: Diabetes is associated with higher risk of death from all causes and cancer. In subjects without diabetes, stage 2 IFG and/or IGT confers increased risk for mortality.

The New Era of Evolution and Innovation in Hanyang Medical Reviews / 한양의대학술지

No abstract available.

Response: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J 2013;37:117-24)

No abstract available.

Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study

BACKGROUND: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS: The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS: Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values < or =6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). CONCLUSION: Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.

Association between Nutrient Intake and Obesity in Type 2 Diabetic Patients from the Korean National Diabetes Program: A Cross-Sectional Study

The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (Ptrend = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (Ptrend = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (Ptrend < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198).

Endocrine Diseases in Diabetes Mellitus / 한양의대학술지

The endocrine pancreas secretes several hormones including insulin and glucagon and dysfunction of them may lead to diabetes mellitus. The integrated regulation of systemic glucose balance prevents the devastating consequences of hypoglycemia and hyperglycemia. This remarkable homeostatic feat is accomplished primarily by hormones, but also by neurotransmitters and substrate effects, and it reflects the interplay of plasma glucose-lowering and glucose-raising factors. Moreover, endocrine diseases frequently co-associate with diabetes mellitus. There have also been several reports on changes in growth hormone (GH) in nutrient excess or deprivation. GH is released into the general circulation where it interacts with multiple peripheral tissues through its receptor, GH receptor, to regulate growth and metabolic function. In humans, GH levels decrease in states of nutrient excess such as obesity, and increase in response to nutrient deprivation such as fasting. Considering that GH regulates metabolism of carbohydrate, lipid, and protein, clarifying the mechanisms by which metabolic changes alter GH synthesis and secretion will increase our knowledge on the pathophysiology and treatment of metabolic diseases. In this review, the effect of nutrient excess and nutrient deficiency on GH axis function in humans will be summarized, with particular emphasis on studies exploring the direct effects of systemic signals, including insulin-like growth factor 1 (IGF-1) and insulin, on somatotrope function. Moreover, there will be a discussion over the overlap syndrome consisting of multiple endocrine neoplasm (MEN) and polyglandular autoimmune diseases (PGA).

Direct Medical Costs for Patients with Type 2 Diabetes and Related Complications: A Prospective Cohort Study Based on the Korean National Diabetes Program

We analyzed the direct medical costs for Korean patients with type 2 diabetes according to the type of complications and the number of microvascular complications. We analyzed costs for type 2 diabetes and associated complications in 3,125 patients. These data were obtained from the Korean National Diabetes Program (KNDP), a large, ongoing, prospective cohort study that began in 2005. The cost data were prospectively collected, using an electronic database, for the KNDP cohort at six hospitals. The costs were analyzed according to complications for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no vascular complications; 1,883 had microvascular complications only; 51 had macrovascular complications only; and 273 had both complications. The annual direct medical costs for a patient with only macrovascular, only microvascular, or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0 times higher than the medical costs of patients without complications. Annual direct medical costs per patient increased with the number of microvascular complications in patients without macrovascular complications. The economic costs for type 2 diabetes are attributable largely to the management of microvascular and macrovascular complications. Proper management of diabetes and prevention of related complications are important for reducing medical costs.

Peptide/Gene Therapy for the Prevention of Diabetes / 한양의대학술지

Pancreatic betacell function deteriorates continuously in type 2 diabetes patients despite optimal treatment, which has been attributed to hyperglycemia itself via formation of excess reactive oxygen species. Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet betacell destruction can be manipulated by the administration of cytokines, especially Th2 cytokines. Restoration of self tolerance at certain time period may facilitate islet cell regeneration and may enable complete recovery from diabetes. To overcome short halflives of cytokines, we would like to deliver genes which enable cytokine production in the body. We also induced antiapoptotic molecules in betacells, the protective effect of which we screened systematically, applying new gene/peptide delivery strategies. In this study, the effect of peptide delivery using specific carriers was evaluated both in vitro and in vivo. In view of the immunoregulatory activity of Th2 cytokines, we investigated whether systemic or local cytokine gene therapy stops islet destructive autoimmunity and regenerates betacells of the pancreas in NOD mice. In addition, treatment of betacells with the antioxidant metallothionein resulted in a significant reduction in pathological changes and restored GSIS. Specific inhibition of NF-kappaB activation by retroviral transduction of dominant negative inhibitor of NF-kappaB also protected betacells. Therefore, these results suggest the protective influence of these gene/ peptide delivery as an adjunctive measure to clinical islet transplantation may enable us to improve the results of the cell-based treatment to overcome the battle against the debilitating disease of diabetes mellitus.

Management of the Patients with Diabetes Mellitus and Macro- and Microvascular Complications

The chronic, mainly vascular complications of diabetes mellitus involve many organs and are responsible for the majority of morbidity and mortality associated with the disease. The vascular complications of diabetes are divided into microvascular and macrovascular complications. Although some macrovascular complications may precede the development of diabetes, they frequently co-associate and present together. The increasing prevalence of diabetes and its association with macrovascular disease have become serious public health concerns. Patients with diabetes who have underlying coronary artery diseases have a different, more complex pathophysiology and a worse prognosis. Optimal management of these patients requires a comprehensive multifactorial approach to prevent microvascular and macrovascular events. In the setting of an acute myocardial infarction (aMI), immediate management should focus on limiting the infarct size using fibrinolytic agents, primary percutaneous intervention, or glycoprotein IIb/IIIa inhibitors. Drug-eluting stents may have an important role in patients with diabetes, who have a higher rate of post-intervention coronary restenosis than in nondiabetic individuals. All patients with aMI should be given aspirin, nitrates, beta-blockers, and angiotensin-converting enzyme inhibitors. Lipid-lowering agents as well as glycemic control have been shown to be effective in decreasing long-term mortality. Despite advances in the management of the vascular complications, the mortality rates of patients with diabetes remain 1.5-to 2-fold greater than those of individuals without diabetes. Maximizing the use of lifesaving therapies proved effective, and a tight metabolic control can further decrease mortality rates. However, many of these lifesaving therapies are underused in patients with diabetes because of the misconception that potential adverse effects may outweigh their benefits. New programs aimed at improving post-infarction quality of care in patients with diabetes, based on guidelines and expert recommendations, have shown promising. However, more efforts should be devoted to the improvement of outcomes related to these public health problems.