BACKGROUND: Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment. METHODS: A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L). RESULTS: The proportion of patients with diabetic retinopathy (DR) (P for trend < 0.001), coronary heart disease (CHD) (P for trend < 0.001), and stroke (P for trend < 0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables. CONCLUSION: Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.
Blood Glucose ; Confounding Factors (Epidemiology) ; Coronary Disease ; Cystatin C* ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy ; Humans ; Retrospective Studies ; Risk Factors ; Stroke

The morbidity and mortality associated with diabetic complications impose a huge socioeconomic burden worldwide. Therefore, the ultimate goal of managing diabetes mellitus (DM) is to lower the risk of macrovascular complications and highly morbid microvascular complications such as diabetic nephropathy (DN) and diabetic retinopathy (DR). Potential benefits of incretin-based therapies such as glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on the diabetic macrovascular complications have been recently suggested, owing to their pleiotropic effects on multiple organ systems. However, studies primarily investigating the role of these therapies in diabetic microvascular complications are rare. Nevertheless, preclinical and limited clinical data suggest the potential protective effect of incretin-based agents against DN and DR via their anti-inflammatory, antioxidative, and antiapoptotic properties. Evidence also suggests that these incretin-dependent and independent beneficial effects are not necessarily associated with the glucose-lowering properties of GLP-1 RAs and DPP-4 inhibitors. Hence, in this review, we revisit the preclinical and clinical evidence of incretin-based therapy for DR and DN, the two most common, morbid complications in individuals with DM. In addition, the review discusses a few recent studies raising concerns of aggravating DR with the use of incretin-based therapies.
Diabetes Complications ; Diabetes Mellitus ; Diabetic Nephropathies ; Diabetic Retinopathy ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Mortality

BACKGROUND: This is part of a prospective study carried out as a national project to secure standardized public resources for type 2 diabetes mellitus (T2DM) patients in Korea. We compared various characteristics of long-standing T2DM patients with diabetic retinopathy (DR) and macular edema (ME). METHODS: From September 2014 to July 2015, T2DM patients with disease duration of at least 15 years were recruited at a single university hospital. Clinical data and samples were collected according to the common data elements and standards of procedure developed by the Korean Diabetes Association Research Council. Each participant was assessed by ophthalmologists for DR and ME. RESULTS: Among 220 registered patients, 183 completed the ophthalmologic assessment. DR was associated with longer disease duration (odds ratio [OR], 1.071; 95% confidence interval [CI], 1.001 to 1.147 for non-proliferative diabetic retinopathy [NPDR]) (OR, 1.142; 95% CI, 1.051 to 1.242 for proliferative diabetic retinopathy [PDR]) and the use of long-acting insulin (OR, 4.559; 95% CI, 1.672 to 12.427 for NPDR) (OR, 4.783; 95% CI, 1.581 to 14.474 for PDR), but a lower prevalence of a family history of cancer (OR, 0.310; 95% CI, 0.119 to 0.809 for NPDR) (OR, 0.206; 95% CI, 0.063 to 0.673 for PDR). ME was associated with higher glycosylated hemoglobin levels (OR, 1.380; 95% CI, 1.032 to 1.845) and the use of rapid-acting insulin (OR, 5.211; 95% CI, 1.445 to 18.794). CONCLUSION: Various clinical features were associated with DR and ME. Additional epidemiological and biorepository-based studies using this cohort are being conducted to deepen our understanding of diabetic complications in Korea.
Cohort Studies ; Common Data Elements ; Diabetes Complications ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy* ; Hemoglobin A, Glycosylated ; Humans ; Insulin, Long-Acting ; Insulin, Short-Acting ; Korea ; Macular Edema ; Prevalence ; Prospective Studies

Both diabetic retinopathy (DR) and coronary heart disease (CHD) are clinically significant in diabetic patients. We investigated the correlation between the severity of DR and the presence and severity of CHD among type 2 diabetic patients. A total of 175 patients who were examined at the DR clinic and underwent dual-source computed tomography (DSCT) angiography within 6 months were included. The degree of DR was graded as no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). The severity of CHD and the numbers of significant stenotic coronary artery on DSCT angiography according to DR grade were assessed. The mean Agatston Calcium Score (ACS) in patients with PDR was significantly higher than other groups (P < 0.001). The overall odds of an ACS increase were about 4.7-fold higher in PDR group than in no DR group (P < 0.001). In PDR group, in comparison with in no DR, the odds of having 1 or 2 arterial involvement were 3-fold higher (P = 0.044), and those of having 3 were 17-fold higher (P = 0.011). The c-index, one of the predictability values in regression analysis model, was not significantly increased when PDR was added to classical CHD risk factors (0.671 to 0.706, P = 0.111). Conclusively, patients with PDR develop a greater likelihood of not only having CHD, but being more severe nature. PDR has no additional effect to classical CHD risk factors for predicting CHD.
Aged ; Angiography ; Coronary Artery Disease/complications/*pathology ; Coronary Vessels/diagnostic imaging ; Diabetes Mellitus, Type 2/*complications ; Diabetic Retinopathy/complications/*diagnosis/diagnostic imaging ; Female ; Glomerular Filtration Rate ; Humans ; Linear Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Severity of Illness Index ; Tomography, X-Ray Computed

Both diabetic retinopathy (DR) and coronary heart disease (CHD) are clinically significant in diabetic patients. We investigated the correlation between the severity of DR and the presence and severity of CHD among type 2 diabetic patients. A total of 175 patients who were examined at the DR clinic and underwent dual-source computed tomography (DSCT) angiography within 6 months were included. The degree of DR was graded as no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). The severity of CHD and the numbers of significant stenotic coronary artery on DSCT angiography according to DR grade were assessed. The mean Agatston Calcium Score (ACS) in patients with PDR was significantly higher than other groups (P < 0.001). The overall odds of an ACS increase were about 4.7-fold higher in PDR group than in no DR group (P < 0.001). In PDR group, in comparison with in no DR, the odds of having 1 or 2 arterial involvement were 3-fold higher (P = 0.044), and those of having 3 were 17-fold higher (P = 0.011). The c-index, one of the predictability values in regression analysis model, was not significantly increased when PDR was added to classical CHD risk factors (0.671 to 0.706, P = 0.111). Conclusively, patients with PDR develop a greater likelihood of not only having CHD, but being more severe nature. PDR has no additional effect to classical CHD risk factors for predicting CHD.
Aged ; Angiography ; Coronary Artery Disease/complications/*pathology ; Coronary Vessels/diagnostic imaging ; Diabetes Mellitus, Type 2/*complications ; Diabetic Retinopathy/complications/*diagnosis/diagnostic imaging ; Female ; Glomerular Filtration Rate ; Humans ; Linear Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Severity of Illness Index ; Tomography, X-Ray Computed

Diabetic Retinopathy ; complications ; epidemiology ; physiopathology ; Humans ; Neurodegenerative Diseases ; epidemiology ; etiology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Risk Factors

OBJECTIVETo observe the prevention and clinical efficacy of combination of Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic retinopathy (DR).

METHODSUsing randomized, double-blind, double simulation, parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM) outpatients were recruited and assigned to the treatment group and the control group, 70 in each group. All patients received basic Western medicine treatment (such as blood glucose and pressure control). Patients in the treatment group took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times per day), while those in the control group took LDP placebos and GLT placebos. All treatment lasted for 24 consecutive months. All subjects were followed-up every month. The general clinical data as sex, age, and metabolic data such as blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected and statistically analyzed.

RESULTSThere was no significant difference in levels of blood glucose, blood pressure, or blood lipid between the two groups (P > 0.05). After treatment the DR incidence rate was significantly lower in the treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P < 0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59), P < 0.05].

CONCLUSIONCombination of LDP and GLT could effectively prevent and treat the development of DR in T2DM patients.

Blood Glucose ; analysis ; Blood Pressure ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Humans ; Phytotherapy ; Tablets

BACKGROUND: The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. METHODS: We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). RESULTS: There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. CONCLUSION: We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes.
Age of Onset* ; Aged* ; Cerebral Infarction ; Creatinine ; Diabetes Complications* ; Diabetic Retinopathy ; Female ; Gangwon-do ; Hemoglobin A, Glycosylated ; Humans ; Incidence ; Male ; Medical Records ; Outpatients ; Prevalence

Management of diabetic complications has been a worldwide major global health issue for decades. Recent studies from many parts of the world indicate improvement in this area. However, it is unknown if such an improvement is being realized in Koreans. Although there is limited information regarding diabetic retinopathy management among Koreans, recent epidemiologic studies have indicated improved screening rates and less frequent visual impairment among type 2 diabetics. Moreover, results achieved with new diagnostic and treatment modalities aimed to improve diabetic retinopathy management are encouraging for both physicians and patients.
Diabetes Complications ; Diabetic Retinopathy* ; Epidemiologic Studies ; Global Health ; Humans ; Mass Screening ; Vision Disorders

BACKGROUND: Type 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications. METHODS: In present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms. RESULTS: Mean age was 62.44+/-10.64 years and mean disease duration was 13.65+/-7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis. CONCLUSION: Our findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.
Alleles ; Body Mass Index ; Cardiovascular Diseases ; Chungcheongbuk-do ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy* ; Dyslipidemias ; Endocrine System ; Endocrinology ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; Insulin ; Lipolysis ; Logistic Models ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol* ; Vitamin D* ; Vitamins*