Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

Changing the patterns of hospitalized diabetic foot ulcer (DFU) over a 5-year period in a multi-disciplinary setting in Thailand.

BACKGROUND: After years of decline, the rate of amputations was reported to increase by 50% in the U.S. population between 2009 and 2015. Few studies have examined the most recent trends in hospitalized diabetic foot ulcer (DFU) in Asian patients. This study aimed to examine recent trends and outcomes in hospitalized DFU at a tertiary diabetes center in Bangkok. METHODS: We conducted a retrospective study from consecutive hospitalized DFU admissions from 2014 to 2018 at Theptarin Hospital, a multi-disciplinary diabetes center, led by diabetologists. RESULTS: During the study period, 290 patients (male 57.4%, age 65.5 ± 13.3 years, T2DM 99.4%, DM duration 18.8 ± 11.5 years, A1C 8.6 ± 2.3%) with 350 admissions were included. DFU were classified into neuropathic wounds (38.0%), ischemic wounds (2.6%), and mixed-type wounds (59.4%). The median length of stay was 8 days. Severe DFU (Wagner grade 3-5) composed 68.3% of all DFU and one-third of patients had prior history of amputations. Complete healing was achieved in 73.5% of the patients. Major amputation was performed in 16 (4.6%) and minor amputation was performed in 78 (22.3%) of all DFU. The mortality rate at 1 year after discharge was 12.0%. Advanced diseases with higher co-morbidities were associated with worse outcomes. When compared with our previous published data from 2009 to 2013, the annual rate of ischemic wounds from peripheral arterial diseases (PAD) and severity of DFU were increased in this study period. The major amputation rate slightly decreased from 6.0 to 4.6% but the minor amputation rate increased from 18.7 to 22.3%. CONCLUSION: The changing trend of DFU provides an excellent outlook into the inadequacies of our current diabetes care systems and global trend of aging population. After considerable successes in reducing major amputations over the past decade, the current analysis revealed a discouraging change in the healing rate of DFU and a stable pattern of major amputation. The prevalence of PAD among Thai patients with DFU increased significantly and affected the results of DFU treatments. Redefined organization of care with multidisciplinary team approach and coordination with referral centers are urgently required to improve outcomes of DFU.

Performance of HbA1c versus oral glucose tolerance test (OGTT) as a screening tool to diagnose dysglycemic status in high-risk Thai patients.

BACKGROUND: Dysglycemic status defined by prediabetes and diabetes is known to be related with future risk of diabetic complications and cardiovascular diseases. Herein, we aimed to determine the diagnostic accuracy of glycated hemoglobin (HbA1c) when compared with oral glucose tolerance test (OGTT) as a reference test in identifying dysglycemic status among high-risk Thai patients receiving care in an out-patient setting. METHODS: An 11-year retrospective cross-sectional study of high-risk Thai patients who underwent OGTT during 2007-2017 was analysed. The OGTT was used as a reference test to identify subjects of dysglycemic status. The diagnostic accuracy of HbA1c and the agreement between HbA1c and OGTT were examined. Validated Thai diabetes risk score, Thai cardiovascular risk score (Thai CV risk score), and visceral fat area (VFA) were also compared in each glycemic status from OGTT as surrogate markers for future diabetes and cardiovascular diseases. RESULTS: A total of 512 subjects (females 60.5%, mean age of 50.3 ± 12.7 years, BMI of 26.5 ± 4.6 kg/m2) were reviewed. Normal glucose tolerance (NGT) was found in 220 patients (43.0%), impaired glucose tolerance (IGT) in 191 patients (37.3%), and diabetes in 101 patients (19.7%). The prevalence of diabetes using OGTT was approximately two times higher than those defined by HbA1c (19.7% versus 11.1%). There were poor agreements between the classifications of prediabetes and diabetes defined by OGTT and HbA1c (Cohen's Kappa 0.154 and 0.306, respectively). Using a cut-off value for HbA1c ≥6.5% as a threshold for HbA1c-defined criteria of diabetes, sensitivity was 32% (95% CI 23-41%) and specificity was 94% (95% CI 92-96%). The optimal cut-off HbA1c value for detecting diabetes by Youden's index was at HbA1c 6.2%. Thai CV risk score was much higher among the OGTT-defined diabetes group when compared with the NGT group (median score 10 vs. 3, p-value < 0.001). CONCLUSIONS: Despite the practicality and validity of HbA1c as a diagnostic test, our study suggested that HbA1c as a screening tool for diabetes in high-risk Thai patients is much inferior to OGTT. With limitations of HbA1c, physicians should continue to advocate OGTT as a screening tool for the identification of dysglycemic status in high-risk Thai patients.

Development of New Lemon-Lime Flavored Beverage for OGTT: Acceptability and Reproducibility.

BACKGROUND: The oral glucose tolerance test (OGTT) is essential procedure in both screening and diagnosis of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes mellitus (DM), but it is not easy to perform because of intense sweetness of the 75-g glucose test beverage causing abdominal discomfort post-testing. Therefore, the new formula of non-carbonated lemon-lime flavored beverage was developed to increase its palatability and better compliance. OBJECTIVE: To develop a new non-carbonated lemon-lime flavored beverage to replace the standard beverage for OGTT Subsequently, the diagnostic value and acceptability between the new formula and the traditional 75-g OGTT formula were compared in healthy subjects. MATERIAL AND METHOD: The new lemon-lime flavored formula was developed to replace the standard beverage for OGTT by adding 1,000 milligram of citric acid and 0.03 gram of lime flavor to 75 gram of anhydrous glucose to a final volume of 300 ml. The study was conducted in 30 healthy subjects who underwent the traditional 75-gram OGTT test and the new formula of OGTT beverage one week later, or vice versa, to access acceptability, indices markers of insulin secretion, and insulin sensitivity. Palatability was determined by rating on a 9-point Hedonic Scale. RESULTS: Thirty healthy subjects (15 females) with the age of 33.2 ± 7.5 years and body mass index of 22.9 ± 3.5 kg/m² were enrolled. No significant difference was found between plasma glucose in 0, 30, 60, 90, and 120 minutes, insulin level (0 and 120 minutes) and four insulin surrogate markers in both traditional 75-gram OGTT and new formula of lemon-lime flavored OGTT beverage. The overall satisfaction score of the new formula OGTT was better when compared with the scores of the traditional OGTT (7.1 ± 1.8 vs. 4.7 ± 2.0). Only one subject complained about abdominal discomfort in both episode of OGTT CONCLUSION: The modified lemon-lime flavored beverage for OGTT demonstrated better acceptance in the subjects without difference in plasma glucose values and OGTT derived parameters responses to OGTT in comparison to the traditional formula.

Metformin-Associated Vitamin B12 Deficiency: An Underrecognized Complication.

Metformin-associated vitamin B12 deficiency is a well-established side effect, especially in patients taking higher doses of metformin or who have existing risk factors. Severe deficiency causes a wide range of systemic disorders. Gait instability, which leads to frequent falling, is usually an underrecognized side effect. Older patients are more likely to develop chronic subdural hematoma even with minor trauma. We present a case of 84-year-old man with type 2 diabetes mellitus with acute-on-chronic subdural hematoma from frequent falls. Metformin therapy at dose of 1700 mg/day was given for more than 25 years. He had been in his usual state of health until 10 months ago when he began to have frequent fallings and fatigue. Physical examination in this admission revealed new-onset impaired vibratory sensation and proprioception in both feet and positive Romberg test. Subsequent evaluations demonstrated undetectable plasma vitamin B12 level and elevated plasma homocysteine. Improvement in neurological symptoms occurred within 1 week of vitamin B12 replacement and surgical hematoma evacuation. This case highlights the importance of awareness and periodic monitoring of vitamin B12 status among older patients taking metformin.

Ectopic Cervical Thymic Tissue Mimicking Parathyroid Hyperplasia: A Rare Occurrence Linked to Graves Disease.

Thymic hyperplasia has occasionally been reported in patients with Graves disease (GD). However, ectopic cervical thymic hyperplasia in the setting of hyperthyroid GD is exceptionally rare. We describe a case of a 54-year-old Thai woman who presented with hyperthyroidism, diplopia, and pretibial myxedema. She underwent a total thyroidectomy because of diplopia caused by Graves ophthalmopathy. During the surgery, 3 macroscopically abnormal enlargements of parathyroid gland-like tissue were identified and removed. Histopathology revealed hyperplastic thymic tissue mixed with 1 normal-sized parathyroid gland at the location of the left upper parathyroid gland, and thymic tissue was found in the sample labeled as the right upper parathyroid gland. Notably, the sample labeled as the right lower parathyroid gland was actually determined to be a lymph node. Preoperative blood samples showed normal serum calcium and parathyroid hormone levels. Postoperatively, computed tomography of the chest showed thymic hyperplasia in the anterior mediastinum, which slightly regressed at the 9-month follow-up. The patient had transient hypoparathyroidism requiring oral calcium and active vitamin D supplements for 6 months postoperatively. Ectopic cervical thymic hyperplasia can be found in GD and might be indistinguishable from parathyroid hyperplasia. Biochemical evaluations are required to exclude concomitant hyperparathyroidism, and a conservative approach should be considered.

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ±â€…13.6 years, mean tumor size 1.6 ±â€…1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ±â€…44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

Prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing.

Background: It is critical to determine the exact type of diabetes because misclassification led to inappropriate treatments. The classification of DM can be aided by the measurement of pancreatic autoantibodies and plasma C-peptide levels. Previous studies suggested that random plasma C-peptide testing in those with clinically diagnosed adult T1DM of at least 3 years duration has led to reclassification in some cases. Aim: This study aimed to assess the prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing. Methods: A cross-sectional study of adult Thai patients diagnosed with clinically diagnosed T1DM and DM duration of at least 3 years at Theptarin Hospital, a diabetes center in Bangkok, Thailand was studied. Clinically misdiagnosis of T1DM was defined by preserved endogenous insulin secretion. Characteristics of the misdiagnosed patients were compared with definite T1DM patients. Results: A total of 73 patients (females 52.1%, mean age 42.2 ± 12.5 years, duration of DM 20.3 ± 11.3 years) were studied. The prevalence of available anti-GAD and anti-IA2 were 53.3% and 20.8%, respectively. Preserved endogenous insulin secretion evaluated by random C-peptide or stimulated C-peptide was found in 8 patients (11.0%). The misdiagnosed patients had higher prevalence of hypertension and diabetic complications. Three patients were suspected to have monogenic diabetes and five patients were reclassified as possible T2DM. Conclusions: Approximately one-tenth of adult T1DM patients were misdiagnosed. Random plasma C-peptide testing at least 3 years after a diagnosis of T1DM was superior to the measurement of pancreatic autoantibodies. Our present study highlights the need to increase accuracy in the diagnosis of T1DM patients by re-assessing endogenous insulin production with measurement of random plasma C-peptide levels.

Real-World Use of Once-Weekly Semaglutide in Thai Patients With Type 2 Diabetes Mellitus in a Private Hospital Setting.

Objective: To evaluate the real-world use of once-weekly semaglutide among Thai patients with type 2 diabetes (T2DM) in a private hospital setting. Methodology: A retrospective review of Thai patients with T2DM who have initiated semaglutide for at least 1 month between June 2020 and March 2022 at Theptarin Hospital, Bangkok, Thailand. Results: A total of 58 patients (50% female, mean age 55.6 ± 15.9 years, with duration of diabetes 12.6 ± 10.3 years, BMI 31.5 ± 4.4 kg/m2, baseline HbA1c 7.9 ± 1.9%, with prior GLP-1 RA use 24.1%, and concomitant SGLT2i intake (41.4%) were included. During a median follow-up of 6 months, the mean serum HbA1c level reduction was 1.3 ± 1.7% with weight loss of 4.7 ± 4.1 kg. The proportion of patients who achieved optimal and sustainable glycemic control (HbA1c < 7.0%) increased from 43.1% to 55.8% at the last follow-up. The proportion of patients reaching both HbA1c targets of <7.0% and 5% weight loss was 27.8%. No cases of pancreatitis, cancer, or progressive retinopathy were observed. Conclusions: In this single center undertaking, it was shown that in among persons with T2DM and obesity in Thailand, semaglutide was associated with short-term glycemic control and weight loss comparable with what has been observed in randomized clinical trials and other RWE.

Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus.

AIMS: To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus. METHODS: KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR. RESULTS: Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus. CONCLUSIONS: Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.

Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes.

Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome-wide methylation patterns are poorly defined. While methylation is known to alter gene expression, the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n = 39) that was subsequently replicated in a larger validation cohort (n = 296). Gene body-related regions made up more than 60% of the methylation differences and emphasized the importance of methylation sequencing. We observed differentially methylated genes associated with DN in 3 independent T1D registries originating from Denmark (n = 445), Hong Kong (n = 107), and Thailand (n = 130). Reduced DNA methylation at CTCF and Pol2B sites was tightly connected with DN pathways that include insulin signaling, lipid metabolism, and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubule cells. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding, and the activation of insulin-signaling phosphoproteins in hyperglycemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophages and vascular endothelial cells.

Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes: a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program.

Background: In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits. Methods: Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m2]). Findings: Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0-12.0) years; mean ± SD HbA1c 8.0 ± 1.9%; 27% insulin-treated), women were older and less likely to receive college education than men (28.9% vs. 48.8%). Women were less likely to smoke/drink alcohol and were physically less active than men. Women had lower BP (<130/80 mmHg: 29.4% vs. 25.7%), less general obesity (54.8% vs. 57.8%) but more central obesity than men (77.5% vs. 57.3%). Women were less likely to have ASCVD (12.8% vs. 17.0%) or heart failure (1.3% vs. 2.3%), but more likely to have kidney impairment (22.3% vs. 17.6%) and any-site cancer than men (2.5% vs. 1.6%). In most countries/areas, more men attained HbA1c <7% and risk-based LDL-cholesterol level than women. After adjusting for potential confounders including countries and centres, men had 1.63 odds ratio (95% CI 1.51, 1.74) of attaining ≥3 treatment targets than women. Interpretation: Asian women with T2D had worse quality of care than men especially in middle-income countries/areas, calling for targeted implementation programs to close these care gaps. Sponsor: Asia Diabetes Foundation. Funding: Nil.

Painless thyroiditis complicating with hypercalcemic encephalopathy.

BACKGROUND: Severe hypercalcemia has rarely been reported in patients with hyperthyroidism. Although the pathogenesis is not clear; it is believed to be due to activation of osteoclasts resulting in excessive bone resorption. OBJECTIVE: To recognize the unusual cause of hypercalcemia from painless thyroiditis, which could manifest with transient hyperthyroidism in the early stage. CASE REPORT: A 70-year-old woman presented with watery diarrhea, nausea and vomiting and significant weight loss for two months. Initially, she was misdiagnosed as having Graves'disease from her clinical presentation and thyroid function tests. Oral propylthiouracil was given to treat hyperthyroidism. However two weeks after discharge, she developed altered consciousness due to severe hypercalcemia. After combined treatment of hypercalcemia and severe hyperthyroidism, her symptoms resolved quickly. Later on, her thyroid function tests switched to subclinical hypothyroid at two months after initial presentation. No concurrent pathological conditions could be found to explain the other causes of hypercalcemia. Therefore, painless thyroiditis complicated with severe hypercalcemia was subsequently diagnosed based on her clinical course. CONCLUSION: Hypercalcemic encephalopathy is an uncommon manifestation of hyperthyroidism that should be kept in mind in patients who demonstrated clinical pictures of hyperthyroidism and alteration of consciousness. Moreover the present case emphasizes the consideration of painless thyroiditis as a differential diagnosis of hyperthyroidism because anti-thyroid medications were not indicated in this condition.

Kratom-Associated Mixed Cholestatic-Hepatocellular Liver Injury in a Patient With Long COVID: A case Report.

Introduction: Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom which led people in many areas to seek income from the sale of kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-COVID syndrome who developed a mixed cholestatic-hepatocellular liver injury secondary to kratom. Case presentation: A 23-year-old Thai man was seen for an evaluation of fatigue and nausea which was soon followed by pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was purchased from a friend and used in a homemade iced cocktail called "4 × 100" consisting of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. His lab workup showed his total bilirubin to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, and alanine aminotransferase was 1635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed normal liver and no cirrhosis. The case was managed conservatively for 5 days in the hospital by giving intravenous fluid and stopping all medications. Urine toxicology screening confirmed the presence of mitragynine and diphenhydramine. He was in a stable condition with normalized liver function tests at 3 months after discharge. Conclusion: The COVID-19 pandemic has posed unprecedented challenges to health consequences and this case highlights the importance of kratom as potential cause of acute liver injury. Future studies should accumulate further case series and identify kratom-user subgroups or the polydrug patterns of kratom use that are at heightened risk of severe liver injury.

Diabetes mellitus and insulin resistance associated with Kabuki syndrome-A case report and literature review.

Kabuki syndrome (KS) is a genetic disorder characterized by distinctive facies, intellectual disability, and multi-organ anomalies. This case report highlights the importance of clinical recognizable phenotype in patients with diabetes. The development of diabetes should be considered an endocrine complication in KS patients.

Hypertriglyceridemia as a main feature associated with 17q12 deletion syndrome-related hepatocyte nuclear factor 1ß-maturity-onset diabetes of the young.

Summary: Hepatocyte nuclear factor 1ß (HNF1B) gene is located on chromosome 17q12. It is a transcription factor implicated in the early embryonic development of multiple organs. HNF1B-associated disease is a multi-system disorder with variable clinical phenotypes. There are increasing reports suggesting that the 17q12 deletion syndrome should be suspected in patients with maturity-onset diabetes of the young type 5 (MODY5) due to the deletion of HNF1B gene. In contrast to classical 17q12 syndrome in childhood with neurological disorders and autism, patients with HNF1B-MODY deletion rarely had neuropsychological disorders or learning disabilities. The diagnosis of 17q12 deletion syndrome highlighted the phenotypic heterogeneity of HNF1B-MODY patients. In this study, we report the clinical course of a Thai woman with young-onset diabetes mellitus and hypertriglyceridemia as a predominant feature due to HNF1B deletion as part of the 17q12 deletion syndrome. Our findings and others suggest that hypertriglyceridemia should be considered a syndromic feature of HNF1B-MODY. Our case also highlights the need to use sequencing with dosage analyses to detect point mutations and copy number variations to avoid missing a whole deletion of HNF1B. Learning points: Maturity-onset diabetes of the young type 5 (MODY5) may be caused by heterozygous point mutations or whole gene deletion of HNF1B. Recent studies revealed that complete deletion of the HNF1B gene may be part of the 17q12 deletion syndrome with multi-system involvement. The length of the deletion can contribute to the phenotypic variability in patients with HNF1B-MODY due to whole gene deletion. Using next-generation sequencing alone to diagnose MODY could miss a whole gene deletion or copy number variations. Specialized detection methods such as microarray analysis or low-pass whole genome sequencing are required to accurately diagnose HNF1B-MODY as a component of the 17q12 deletion syndrome. Molecular diagnosis is necessary to distinguish other acquired cystic kidney diseases in patients with type 2 diabetes which could phenocopy HNF1B-MODY. Hypertriglyceridemia is a possible metabolic feature in patients with HNF1B-MODY due to 17q12 deletion syndrome.

Profile of Levothyroxine Replacement Therapy in Graves' Disease Patients with Hypothyroidism Post-Radioactive Iodine Ablation: Focus on Different Weight-Based Regimens.

Objective: To evaluate the status of euthyroidism achieved among Thai patients with post-ablative hypothyroidism and to examine the difference between various weight-based daily levothyroxine (LT4) replacement regimens in these patients. Methodology: We conducted a retrospective review of Thai patients with Graves' disease (GD) who developed hypothyroidism following radioactive iodine treatment from 2016 to 2020 at Theptarin hospital. Daily LT4 dose was calculated based on actual body weight (ABW), ideal body weight (IBW), and estimated lean body mass (LBM). Results: We reviewed a total of 271 patient records. Of these, 81.2% were females with a mean age of 40.8±11.7 years, LT4 intake duration of 27.1±14.6 months, and LT4 dose/kg ABW of 1.4±0.5 µg/kg/day. At the final follow-up, 62.4% of patients achieved thyroid-stimulating hormone (TSH) levels within the reference interval, 15.5% had TSH levels over, and 22.1% had TSH levels under the reference range. Obese patients required a lower daily LT4 dose relative to ABW and higher daily LT4 dose relative to IBW to attain euthyroidism (ABW 1.1±0.4 µg/kg/day and IBW 2.0±0.8 µg/kg/day). Estimated daily LT4 dose based on LBM showed a constant dosage of 2.0 µg/kg/day in all BMI categories. Conclusions: Suboptimum LT4 replacement therapy was found in almost half of hypothyroid patients with GD treated with radioactive iodine. Estimated LBM was a better indicator for dosing calculation in these patients compared with ABW and IBW.

Effect of a Web-Based Management Guide on Risk Factors in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A JADE Randomized Clinical Trial.

Importance: Diabetic kidney disease (DKD) and its comorbidities can be prevented by treating multiple targets. Technology-assisted team-based care with regular feedback and patient empowerment can improve the attainment of multiple targets and clinical outcomes in patients with type 2 diabetes, but the effects of this intervention on patients with DKD are unclear. Objective: To evaluate the effect of the Joint Asia Diabetes Evaluation (JADE) web portal, nurse reminders, and team-based care on multiple risk factors in patients with DKD. Design, Setting, and Participants: This 12-month multinational, open-label randomized clinical trial was conducted between June 27, 2014, and February 19, 2019, at 13 hospital-based diabetes centers in 8 countries or regions in Asia. All patients who participated had DKD. The intention-to-treat data analysis was performed from April 7 to June 30, 2020. Interventions: Patients were randomized in a 1:1:1 ratio at each site to usual care, empowered care, or team-based empowered care. All patients underwent a JADE web portal-guided structured assessment at baseline and month 12. Patients in the usual care and empowered care groups received a medical follow-up. Patients in the empowered care group also received a personalized JADE report and nurse telephone calls every 3 months. Patients in the team-based empowered care group received additional face-to-face reviews every 3 months from a physician-nurse team. Main Outcomes and Measures: The primary outcome was the proportion of patients who attained multiple treatment targets (defined as ≥3 of 5 targets: HbA1c level <7.0% [53 mmol/mol], blood pressure <130/80 mm Hg, low-density lipoprotein cholesterol level <1.8 mmol/L, triglyceride level <1.7 mmol/L, and/or persistent use of renin-angiotensin-aldosterone system inhibitors). Results: A total of 2393 patients (mean [SD] age, 67.7 [9.8] years; 1267 men [52.9%]) were randomized to the usual care group (n = 795), empowered care group (n = 802), and team-based empowered care group (n = 796). At baseline, 34.7% patients (n = 830) were on 3 treatment targets. On intention-to-treat analysis, the team-based empowered care group had the highest proportion of patients who had further increase in attainment of multiple treatment targets (within-group differences: usual care group, 3.9% [95% CI, 0.0%-7.8%]; empowered care group, 1.3% [95% CI, -2.8% to 5.4%]; team-based empowered care group, 9.1% [95% CI, 4.7%-13.5%]). The team-based empowered care group was more likely to attain multiple treatment targets than the usual care group (risk ratio [RR], 1.17; 95% CI, 1.00-1.37) and the empowered care group (RR, 1.25; 95% CI, 1.06-1.48) after adjustment for site. Compared with the group that did not attain multiple treatment targets, the group that attained multiple treatment targets reported a lower incidence of cardiovascular, kidney, and cancer events (8.4% [n = 51] vs 14.5% [n = 134]; P = .004). Analysis of the per-protocol population yielded similar results. Conclusions and Relevance: This trial found that technology-assisted team-based care for 12 months improved the attainment of multiple treatment targets as well as empowerment in patients with DKD. Trial Registration: ClinicalTrials.gov Identifier: NCT02176278.

Unilateral gynecomastia as an initial presentation of hyperthyroid Graves' disease.

SUMMARY: Graves' disease is an autoimmune condition leading to the activation of and an increase in thyroid hormone secretion. Manifestations of hyperthyroidism in Graves' disease can vary among people. In this case, we report a 24-year-old Thai man with a rare presentation of unilateral gynecomastia along with symptoms of thyrotoxicosis. Physical examination revealed a 3 cm non-tender palpable glandular tissue beneath and around the left areola without nipple discharge and moderately diffuse thyroid enlargement with thyroid bruit. Thyroid function test showed a typical thyrotoxicosis state with elevated serum-free T4 and decreased serum TSH. His diagnosis of Graves' disease was confirmed biochemically with a highly elevated anti-TSH receptor antibody. Early treatment with anti-thyroid medication was given first, followed by Radioiodine treatment (RAI) for definitive treatment due to high level of anti-TSH receptor antibody, enlarged thyroid and severe thyrotoxicosis presentation at a young age, which might not resolve by anti-thyroid medication alone. The patient responded well to treatment and achieved complete resolution of unilateral gynecomastia with clinically and biochemically euthyroid within 3 months after treatment. No recurrent gynecomastia was found during the 2-year follow-up. LEARNING POINTS: Characteristic of gynecomastia in hyperthyroidism is usually presented with bilateral progressive gynecomastia; however, unilateral gynecomastia is occasionally found as a presentation of hyperthyroidism. Complete resolution of gynecomastia without recurrence can be achieved within a few months of treatment after thyrotoxicosis is resolved in patients with hyperthyroidism with the recent development of gynecomastia. RAI for definitive treatment is recommended in young adult patients expressing very high anti-TSH antibody level with severe thyrotoxicosis.

Celiac Disease as a Cause of Anemia and Brittle Diabetes in Type 1 Diabetes Mellitus.

Untreated celiac disease (CD) leads to an increased risk for hypoglycemia and diabetic complications. However, the diagnosis of CD can be challenging and some extra-gastrointestinal tract manifestations could be a presenting symptom. We report a case of a 29-year-old Indian male with brittle T1DM whose underlying CD was discovered from a work-up for anemia. After an introduction of a gluten-free diet, he gained 5 kgs in two months, was responsive to oral iron supplement, and had stable glycemic control with much less hypoglycemia. Even though this disease is rare in Asian populations, the diagnosis of celiac disease should always be kept in mind when people with T1DM present with unexplained microcytic anemia and/or unexplained hypoglycemia.