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

BACKGROUND/OBJECTIVES: Diabetes is diagnosed after an average of 10–12 years of diabetic development. Strict glycemic control in diabetic patients promotes the normalization of blood glucose and reduces cardiovascular diseases (CVDs) and diabetic complications. Therefore, early diagnosis in non-aware individuals is very important. SUBJECTS/METHODS: Clinical indices and nutrient intakes in Korean diabetic adults aged 19–64 years were examined according to the awareness of diabetes, using 2012 and 2013 Korea National Health and Nutrition Examination Survey (KNHANES) data. The aware group was defined as individuals who were aware of having diabetes from diagnosis by physician before the survey and the non-aware group as individuals who were not aware of having diabetes. RESULTS: The average age was higher in the aware group compared to the non-aware group in both men (P = 0.002) and women (P = 0.004). The prevalences of hypertension and dyslipidemia were not different between the two groups, but the diagnosis rate was significantly lower in the non-aware group. In the non-aware group, total and LDL-cholesterol were significantly higher (P < 0.001), the risk for total cholesterol over 240 mg/dL was 3.4 times (95% CI: 1.58–7.52) higher (P = 0.002) and the risk for LDL-cholesterol over 160 mg/dL was 4.59 times (95% CI: 2.07–10.17) higher (P < 0.001). The calorie intake of the female non-aware group was significantly higher compared to the female aware group (P = 0.033). CONCLUSION: The results suggested that the recommendation of screening test is necessary even for young adults. Studies on the methodology for early diagnosis of diabetes are also needed.
Adult ; Blood Glucose ; Cardiovascular Diseases ; Cholesterol ; Diabetes Complications ; Diagnosis ; Dyslipidemias ; Early Diagnosis ; Female ; Humans ; Hypertension ; Korea ; Male ; Mass Screening ; Nutrition Surveys ; Prevalence ; Young Adult

The present article demonstrates an unusual case of bilateral lower extremity edema caused by neurogenic areflexic bladder as the first physical symptom of diabetes. A 52-year-old man presented to the emergency department because of massive edema of his lower limbs. The edema had been present for 2 weeks, was symmetrical, and was progressively covering the lower limbs up to the inguinal area, scrotal bag, and penis and was accompanied by dysuria and an interrupted urine stream. Laboratory findings revealed a serum glucose level of 657 mg/dL and glycated hemoglobin (HbA1c) level of 15.6%. Computed tomography (CT) of the abdomen and pelvis revealed marked enlargement of the bladder with bilateral hydronephrosis and hydroureter. In addition, CT demonstrated bilateral compression of the iliac veins caused by the enlarged bladder. This case highlights the importance of a broad differential diagnosis for patients with diabetes and extensive peripheral edema. Neurogenic bladder should be considered in the differential diagnosis, even in newly diagnosed diabetic patients.
Abdomen ; Blood Glucose ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Diagnosis, Differential ; Dysuria ; Edema ; Emergency Service, Hospital ; Hemoglobin A, Glycosylated ; Humans ; Hydronephrosis ; Iliac Vein ; Lower Extremity ; Male ; Middle Aged ; Pelvis ; Penis ; Rivers ; Urinary Bladder ; Urinary Bladder, Neurogenic

BACKGROUND: There have been equivocal results in studies of the effects of dipeptidyl peptidase-4 inhibitors (DPP-4i) on fractures. In this study, we analyzed the effect of DPP-4i on bone fracture risk in a Korean population. METHODS: We extracted subjects (n = 11,164) aged 50 years or older from the National Health Insurance Service–National Sample Cohort 2.0 from 2009 to 2014. Our control group included subjects without diabetes (n = 5,582), and our treatment groups with diabetes included DPP-4i users (n = 1,410) and DPP-4i non-users (n = 4,172). The primary endpoint was the incidence of a composite outcome consisting of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures. The secondary endpoint was the incidence of each individual component of the composite outcome. Survival analysis was performed with adjustment for age, gender, diabetes complications severity index, Charlson comorbidity index, hypertension medication, and dyslipidemia treatment. RESULTS: The incidence of the composite outcome per 1,000 person-years was 0.089 in DPP-4i users, 0.099 in DPP-4i non-users, and 0.095 in controls. There was no significant difference in fracture risk between DPP-4i users and DPP-4i non-users or controls after the adjustments (P > 0.05). The incidences of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures were not significantly different between DPP-4i users and non-users. The results of subgroup analyses by gender and age were consistent. CONCLUSION: DPP-4i had no significant effect on the risk of fractures in a Korean population.
Cohort Studies ; Comorbidity ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Diagnosis ; Dipeptidyl-Peptidase IV Inhibitors ; Dyslipidemias ; Femoral Fractures ; Fractures, Bone ; Hypertension ; Incidence ; National Health Programs ; Osteoporosis ; Osteoporotic Fractures

Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
Adult* ; Autoantibodies ; C-Peptide ; Diabetes Complications ; Diabetes Mellitus, Type 1* ; Diabetes Mellitus, Type 2 ; Diagnosis ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Phenotype ; Population Characteristics

Diabetic ketoacidosis (DKA) is serious complication of diabetes mellitus that requires prompt recognition, diagnosis and treatment. It is characterized by a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration. The overall DKA mortality rate recorded among children and adults is < 1%. For patients with DKA, appropriate administration of intravenous fluids and insulin with attention to associated fluid and electrolyte disorders can effectively and rapidly resolve metabolic dysregulation. Following acute management and restoration of physiological glucose levels, DKA requires identification of the precipitating cause to prevent recurrence of potentially life-threatening diabetic complications.
Acidosis ; Adult ; Child ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Ketoacidosis* ; Diagnosis ; Glucose ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Mortality ; Recurrence

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and is diagnosed as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes. The prevalence of DPN was reported at 33.5% of type 2 diabetes patients by the Korean diabetes neuropathy study group. Early diagnosis is recommended to prevent diabetic foot ulcers, amputation, or disability. A questionnaire asking about symptoms and neurologic examination of feet is commonly used as a screening tool. However, complete diagnostic tests for DPN are not well established because of incomplete understanding of the pathogenetic mechanisms leading to the nerve injury, the various clinical manifestations, and the unclear natural history. Therefore, DPN has not been paid sufficient attention by clinicians. The roles of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are well known. Pathogenetically oriented or symptomatic agents are other options, though such treatments do not always produce a satisfactory outcome. Therefore, DPN remains a challenge for physicians to screen, diagnose, and treat. There have been recent advances in understanding the mechanisms underlying DPN and in the development of new diagnostic modalities and treatments. In this review, diagnosis and management of DPN will be discussed.
Amputation ; Diabetes Complications ; Diabetic Foot ; Diabetic Neuropathies ; Diagnosis* ; Diagnostic Tests, Routine ; Early Diagnosis ; Foot ; Humans ; Mass Screening ; Natural History ; Neurologic Examination ; Peripheral Nerves ; Peripheral Nervous System Diseases* ; Prevalence ; Risk Factors ; Ulcer

To investigate the clinical features of the recurrence of idiopathic benign paroxysmal positional vertigo(IBPPV)patients.Patients with IBPPV were enrolled and were followed-up for 36 months after being well controlled.The data of the patients including age,gender,and co-morbidities(hypertension,diabetes,hyperlipidemia)were analyzed.Characteristics of the patients with recurrent BPPV were compared with those without recurrence.Two hundred and one patients were enrolled and twenty-two(10.9%)patients presented recurrent IBPPV within 36 months.Among them,about 16% showed changes in the involved semicircular canals.50% recurrence occurred within 6 months after the first treatment.The recurrence rate of BPPV in 50-60 years old patients(50%)is higher than other patients(P=0.04).No significant difference in terms of gender or co-morbidities(hypertension,diabetes,hyperlipidemia)was observed between the two groups.The incidence of recurrence in idiopathic BPPV patients was 10.9%in the present study.The mean period of 50% recurrence after a symptom-free interval was about 6 months.Furthermore,different semicircular canals were involved in about 50% of patients during recurrence.BPPV recurrence was not correlated with age,gender or co-morbiditie.
Benign Paroxysmal Positional Vertigo ; complications ; diagnosis ; Comorbidity ; Diabetes Complications ; Diabetes Mellitus ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Recurrence ; Retrospective Studies ; Semicircular Canals

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.
Biomarkers, Tumor ; genetics ; Carcinoembryonic Antigen ; genetics ; Case-Control Studies ; Colorectal Neoplasms ; complications ; diagnosis ; genetics ; Diabetes Mellitus ; genetics ; GPI-Linked Proteins ; genetics ; Heat-Shock Proteins ; genetics ; Histone Deacetylase 1 ; genetics ; Humans ; Hyperglycemia ; complications ; diagnosis ; genetics ; NADPH Oxidase 1 ; genetics ; ROC Curve