OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

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

PURPOSE: The purpose of this study was to evaluate whether any stage of diabetic retinopathy (DR) is associated with levels of plasma erythropoietin and other plasma parameters. METHODS: It was examined a representative sample of 180 type 2 diabetes patients aged 40 to 79 years. Ophthalmic examination including a funduscopic examination, performed by an experienced ophthalmologist and the retinal finding were classified according to the grading system for diabetic retinopathy of ETDRS (Early Treatment Diabetic Retinopathy Study). It was measured the levels of plasma erythropoietin, cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, fasting blood glucose and hemoglobin A1C (HbA1C) in 88 DR patients and 92 controls without DR. Risk factors correlated with DR were compared between groups. RESULTS: The study group of 180 patients included 72 males and 108 females. The mean age of the patients with and without DR was 57.36 ± 8.87 years and 55.33 ± 8.28 years, respectively. Of the 88 patients with DR, only 9 (10%) had proliferative DR and the rest suffered from non-proliferative DR. The mean plasma levels of erythropoietin in proliferative DR group showed a significant difference in comparison to other groups. The mean plasma levels of cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, and fasting blood glucose were not significantly different in the three groups except for HbA1C. The absolute relative risk (ARR) also showed that erythropoietin was an increasing risk for proliferative DR (ARR, 1.17; 95% confidence interval, 1.060 to 1.420; odds ratio,1.060). CONCLUSIONS: Of the factors studied, erythropoietin level showed significant increase in proliferative DR group. The stepwise raised in mean plasma erythropoietin level which demonstrates significant correlation with proliferative DR versus remaining two groups, will be an indication of its role in proliferative DR.
Adult ; Aged ; Blood Glucose/metabolism ; Cholesterol/blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications ; Diabetic Retinopathy/*blood/diagnosis/*epidemiology ; Enzyme-Linked Immunosorbent Assay ; Erythropoietin/*blood ; Female ; Fluorescein Angiography ; Hemoglobin A, Glycosylated/metabolism ; Humans ; Male ; Middle Aged ; Risk Factors

This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.
Adolescent ; Body Mass Index ; Body Weight ; C-Peptide/*blood ; Child ; Child, Preschool ; Diabetes Complications ; Diabetes Mellitus, Type 1/blood/*diagnosis ; Diabetic Ketoacidosis/epidemiology ; Diabetic Retinopathy/epidemiology ; Female ; Follow-Up Studies ; Hemoglobin A, Glycosylated/analysis ; Humans ; Incidence ; Infant ; Male ; Peripheral Nervous System Diseases/epidemiology ; Retrospective Studies

This cross-sectional study was done to identify and determine the socio-demographic and health-related factors associated with diabetic retinopathy and nephropathy screening in Korea. Participants included 2,660 adults, aged 40 or older, with diabetes. Of the 2,660 adults, 998 (37%) and 1,226 (46.1%) had received a diabetic retinopathy and a nephropathy screening within one year, respectively. Regarding retinopathy, subjects older than 65, living in urban areas, with high educational levels, and with self-reported "unhealthy" status were likely to receive annual screening. Subjects living in urban areas, with higher educational levels, with self-reported "fair" or "unhealthy" status, and with 1 to 2 co-morbidities were likely to receive annual nephropathy screening. The Korea Composite Stock Price Index (KOSPI) continued to rise until 2007 when it started to decline over the subsequent years, following the same curve as the diabetic retinopathy and nephropathy screening rates during that time. Together with the financial matter, lack of patient education proved to be a hindrance to diabetes-related screening. The relatively low screening rates in Korea compared to the Western countries are likely to be due to the difference in the health system, economic situations and national demographics.
Adult ; Aged ; Cross-Sectional Studies ; Diabetes Complications/pathology ; Diabetes Mellitus/diagnosis ; Diabetic Nephropathies/diagnosis/*etiology ; Diabetic Retinopathy/diagnosis/*etiology ; Female ; Health Behavior ; Health Status ; Humans ; Male ; Mass Screening ; Middle Aged ; Nutrition Surveys ; Odds Ratio ; Republic of Korea ; Risk Factors ; Severity of Illness Index

PURPOSE: To compare the efficacy between intravitreal bevacizumab and combination treatment (bevacizumab and macular photocoagulation) for the treatment of diabetic macular edema (DME). In addtion, changes of DME type were researched using optical coherence tomography. METHODS: The present study included 90 eyes with bevacizumab injection and 38 eyes with combination treatment. Using chart records, patients were reviewed until 6 months after treatment. The present study compared changes of visual acuity (VA) and macular thickness at each follow up. DME was classified into 4 types and the morphologic pattern was compared. RESULTS: In patients with the bevacizumab injection only, VA improved from 0.29 +/- 0.18 to 0.48 +/- 0.26 at 1 month and returned to 0.32 +/- 0.20 at 6 months after treatment. In the combination treatment, VA improved from 0.32 +/- 0.22 to 0.52 +/- 0.26 at 1 month and returned to 0.36 +/- 0.18 at 6 months after treatment. There was no significant improvement of VA at the final follow-up with either treatment. There was significant decrease of macular thickness except in the mixed DME type. CONCLUSIONS: The combination treatment did not yield better VA or macular thickness reduction at 6 months than bevacizumab injection alone. By classifying and observing the change of DME type, determining the treatment objectively and predicting the effectiveness of treatment can be helpful.
Angiogenesis Inhibitors/administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Diabetic Retinopathy/*complications/diagnosis/therapy ; Dose-Response Relationship, Drug ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; Humans ; Intravitreal Injections ; Laser Coagulation/*methods ; Macular Edema/diagnosis/etiology/*therapy ; Male ; Microscopy, Acoustic ; Middle Aged ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

PURPOSE: To compare the efficacy between intravitreal bevacizumab and combination treatment (bevacizumab and macular photocoagulation) for the treatment of diabetic macular edema (DME). In addtion, changes of DME type were researched using optical coherence tomography. METHODS: The present study included 90 eyes with bevacizumab injection and 38 eyes with combination treatment. Using chart records, patients were reviewed until 6 months after treatment. The present study compared changes of visual acuity (VA) and macular thickness at each follow up. DME was classified into 4 types and the morphologic pattern was compared. RESULTS: In patients with the bevacizumab injection only, VA improved from 0.29 +/- 0.18 to 0.48 +/- 0.26 at 1 month and returned to 0.32 +/- 0.20 at 6 months after treatment. In the combination treatment, VA improved from 0.32 +/- 0.22 to 0.52 +/- 0.26 at 1 month and returned to 0.36 +/- 0.18 at 6 months after treatment. There was no significant improvement of VA at the final follow-up with either treatment. There was significant decrease of macular thickness except in the mixed DME type. CONCLUSIONS: The combination treatment did not yield better VA or macular thickness reduction at 6 months than bevacizumab injection alone. By classifying and observing the change of DME type, determining the treatment objectively and predicting the effectiveness of treatment can be helpful.
Angiogenesis Inhibitors/administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Diabetic Retinopathy/*complications/diagnosis/therapy ; Dose-Response Relationship, Drug ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; Humans ; Intravitreal Injections ; Laser Coagulation/*methods ; Macular Edema/diagnosis/etiology/*therapy ; Male ; Microscopy, Acoustic ; Middle Aged ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

PURPOSE: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular edema. METHODS: In a retrospective study, 44 eyes with diffuse diabetic macular edema were treated with an intravitreal injection of 4 mg (n=12 eyes), 8 mg (n=17) or 25 mg (n=15) of triamcinolone acetonide (TA). Optical coherence tomography, best-corrected logMAR visual acuity and Goldmann tonometry were performed at baseline, 1 week, and 1, 3, 6, 9 and 12 months after treatment. Mean follow-up was 9.8 months (standard deviation=2.3) with a range of 5-12 months. RESULTS: The duration of intravitreal TA effects on macular thickness and visual acuity increased with increasing dosage. An observed increase in intraocular pressure induced by TA was not significantly associated with dosage. CONCLUSIONS: In patients with diffuse diabetic macular edema who receive intravitreal TA, effects may last longer after a dosage of 25 mg, than after lower doses of 8 mg or 4 mg.
Adult ; Aged ; Aged, 80 and over ; Diabetic Retinopathy/*complications/drug therapy/pathology ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Glucocorticoids/*administration & dosage ; Humans ; Injections ; Intraocular Pressure ; Macular Edema/diagnosis/*drug therapy/etiology ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Treatment Outcome ; Triamcinolone Acetonide/*administration & dosage ; Visual Acuity ; Vitreous Body