Long-Term Sulfonylurea Use and Impaired Awareness of Hypoglycemia Among Patients With Type 2 Diabetes in Taiwan.

PURPOSE: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. METHODS: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. RESULTS: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. CONCLUSIONS: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.Annals Early Access article.

Safety and efficacy in early insulin initiation as comprehensive therapy for patients with type 2 diabetes in primary health care centers.

AIM: to analyze the safety and efficacy of early insulin initiation therapy for patients with type 2 diabetes mellitus (T2DM) in primary health care provided by general practitioners (GPs) in Surabaya, East Java, Indonesia. METHODS: pre-post study of ninety nine diabetic patients without previous insulin treatment with HbA1c levels >8% were involved in this study. The study was conducted in 10 primary health care centers in Surabaya between October 2011 to June 2012. Each patient received insulin therapy for 12 weeks. Laboratory examination was performed for each patient including fasting plasma glucose (FPG), 2 hours post-prandial plasma glucose (2hPPG) and HbA1c examination before and after the study. Self monitoring blood glucose (SMBG) examination was conducted in order to adjust the insulin dose and prevent the incidence of hypoglycemia. Data was statistically analyzed using paired-T test. RESULTS: FPG level was decreased from baseline data (209 mg/dL) to 152.07 mg/dL at the end of the study (56.93 mg/dl; p=0.0001). The average of 2hPPG level was also decreased from 313.00 mg/dl to 220.72 mg/dL ( 92.28 mg/dL; p=0.0001). HbA1c was reduced from 11.60% at baseline to 8.95% at the end of study ( 2.65%; p=0.0001). Hypoglycemia was found in 6 patients (6.06%) in this study, but all events were mild and did not need to be admitted to hospital. CONCLUSION: the safety of insulin therapy iniatiation might be provided by GPs at primary health centers with significant efficacy and minimal side effects.

Unusual Presentations of Thyrotoxic Tricuspid and Mitral Regurgitations in 62 Adults: A Systematic Review of Case Reports with In-depth Pathophysiological Review.

Background: Thyrotoxicosis is related to cardiovascular mortality. This can be caused by several clinical manifestations involving the rare provocation of tricuspid regurgitation (TR) and mitral regurgitation (MR). However, there are still no clear data on thyrotoxic TR and/or MR. This study examines the progression of TR, MR, heart failure (HF) and pulmonary hypertension (PH) in response to the thyrotoxic heart manifestations, clinical characteristics and treatment approaches. Methods: A PRISMA-based systematic search was conducted using PubMed and other databases up to 17 June 2023. The outcomes of this study were TR, MR, HF and PH with their progression on follow-up, clinical characteristics and treatment approaches. Results: A total of 57 case reports involving 62 patients (45.77 ± 13.41 years) were included in this study. They were predominantly women (n=50; 80.65%) and diagnosed with Graves' disease (n=41; 75.81%). All patients were diagnosed with thyrotoxicosis, and this included 23 (37.10%) cases of thyroid storm. From echocardiographic studies, several patients improved clinically within the first 6 months of follow-up, including 20 TR patients (83.33%) in 6 months, nine MR patients (69.23%) in 3 months, eight HF patients (66.67%) in 2 months and 16 PH patients (76.19%) in 6 months. Conclusion: Several mechanisms are involved in thyrotoxic TR and/or MR, including the direct thyroid hormone effect and the indirect effect of other hyperthyroidism-associated factors. Patients with thyrotoxic TR and/or MR, including those with HF and PH, can experience clinical and structural improvements following hyperthyroidism treatment in the first 6 months.

An Indonesian adult with obesity hypoventilation syndrome: a case report.

Obesity hypoventilation syndrome (OHS) is an often overlooked and limited case with other conditions that can cause hypoventilation. Case presentation: An Indonesian female, 22 years old, always feels sleepy, has difficulty concentrating and controlling her appetite. The patient had a fever, respiratory rate of 32 ×/min, pulse rate of 115 ×/min, apathy, obesity (BMI =46.6 kg/m2), and she used oxygen therapy with a non-rebreathing mask of 10 l/min (SO2 of 89%). The patients had daytime hypercapnia & alveolar hypoventilation without other causes of hypoventilation. She was likely to have a chronic condition with relatively stable symptoms that had fallen into a state of acute on chronic hypercapnic respiratory failure. The patient used mechanical ventilation and received supportive management. After 19 days of treatment, the patient's condition improved, and it was recommended to lose weight gradually. In 1-week post hospitalization, the patient experienced a weight loss of 5 kg. Discussion: Mechanical ventilation, supportive management, and decreased body weight of 25-30% gradually have improved prognosis in OHS patients. Bariatric surgery is carried out when the patient cannot lose weight with diet and exercise. Conclusion: OHS management includes oxygen therapy and gradually decreased body weight.

Factors associated with disease severity of COVID­19 in patients with type 2 diabetes mellitus.

Diabetes mellitus causes a decline in immunological function, an increase in proinflammatory cytokines, and a prothrombotic state, thus providing risk factors for the severity of coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to analyze the risk factors associated with the severity of COVID-19 in patients with T2DM. A cross-sectional observational study was performed on 201 patients with T2DM from May 1 to August 31, 2020 and admitted to the isolation ward of Dr Soetomo General Hospital (Surabaya, Indonesia). The patients were divided into severe (108 cases; 53.7%) and non-severe (93 cases; 46.3%) groups, which were considered the dependent variables. Univariate and multivariate analysis was performed. The independent variables were age, sex, diabetes onset, chronic complications, presence of hypertension, randomized blood glucose, HbA1c, albumin, and neutrophil-lymphocyte ratio (NLR). A P-value <0.05 was considered to be statistically significant. The median age of the 201 subjects was 56 years, with 70.1% <60 years old, 52.7% male, 76.1% with diabetes onset <10 years, and 108 patients (53.7%) in severe condition. The results of the bivariate analysis revealed that diabetes onset >10 years (OR 2.5; P=0.011) was associated with severity of COVID-19 in patients with T2DM, however hypoalbumin (OR 1.93; P=0.054) was not associated with disease severity. Furthermore, multivariate analysis revealed that male sex (OR 2.07; P=0.042), age (≥60 years) (OR 2.92; P=0.008), HbA1c (≥8%) (OR 3.55; P=0.001), hypertension (OR 4.07; P=0.001), and an NLR ≥7.36 (OR 6.39; P=0.001) were associated with severe COVID-19. Collectively, it was revealed that increased NLR, hypertension, poor glycemic control, older age, and male sex were risk factors associated with the severity of COVID-19 among diabetic patients.

An Indonesian adolescent with Turner syndrome and ß-thalassemia in low-resource setting: A case report and literature review article.

Background: Turner syndrome and ß-thalassemia very rarely occur together in an individual. Case presentation: An Indonesian adolescent, 18 years old, complained is fatigue a week ago. She has a medical history of ß-thalassemia for age 6 months and Turner syndrome identification for age 16 years. Meanwhile, she regular consumes deferasirox 500 mg every day. Physical examination showed pale conjunctiva and pale face. Body view similar children aged 13 years old. Laboratories investigation values included Hb of 7.7 gr/dL, MCV of 79.5 fL, MCH of 25.9 pg, MCHC of 28.6%, WBC of 6780/mm3, PLT of 242,000/mm3, AST of 15 U/L, ALT of 20 U/L, Ferritin of 1692.32 ng/mL, growth hormone of 0.468 ng/mL, Estradiol of <11.80 pg/mL, luteinizing hormone of 53.50 mIU/mL, and follicle-stimulating hormone of 115.19 mIU/mL. Chromosomal analysis showed Turner syndrome. The patient received a packed red cell transfusion of up Hb of 10 gr/dL, deferasirox 500 mg daily, and a contraceptive tablet. Due to financial issue in Indonesia, patient with Turner syndrome does not get proper hormonal therapy such as growth hormone, vitamin D supplementation, and other hormone replacement therapy. Discussion: Turner syndrome and thalassemia in low-resource settings are challenges in themselves, so in their implementation, only thalassemia can be controlled, but for therapy, it does not show an improvement in prognosis. Conclusion: Turner syndrome and thalassemia both worsen the patient's condition.

An Indonesian male with congenital hypogonadotropic hypogonadism: A case report and literature review.

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by insufficient gonadotropin-releasing hormone (GnRH) production. Case presentation: An Indonesian adolescent, 22 years old, Javanese ethnic, complained of a small penis, low sexual desire, fatigue, and anosmia since childhood. Medical history stated that the patient had low testosterone levels 7 years ago and received testosterone once. Testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were decreased. The testicular ultrasound result was bilateral microtestis, suspicious of bilateral hypoplasia of the epididymis. Brain MRI also supports the diagnosis of hypogonadotropic hypogonadism, and the patient received Sustanon of 250 mg/2 weeks. The patient showed a good prognosis after 1 month of therapy. Discussion: The success of CHH therapy must be explored to improve its management. Conclusion: CHH in an Indonesian male shows a good prognosis with testosterone injection.

Necrotizing fasciitis in Indonesian adult with diabetes mellitus: Two case and review article.

BACKGROUND: Necrotizing fasciitis (NF) is a rare and life-threatening form of infection involving rapidly spreading inflammation and extensive necrosis of the skin, subcutaneous tissue, and superficial fascia. CASE PRESENTATION: This study reported two cases of NF in a 56-year-old female and a 38-year-old male who demonstrated typical signs and symptoms of NF. Both presented to the hospital with skin necrosis in the lower extremity, sepsis shock, and multiorgan failure. Based on the clinical presentation, physical examination, and additional examination, a diagnosis of NF was made. The LRINEC score was used to distinguish NF from other soft tissue infections. Both patients were treated with empirical antibiotics, surgical debridement and planned to be amputated, but the patients were hemodynamically unstable and passed away before the amputation proceeded. DISCUSSION: Delay in the diagnosis of NF increases the risk of mortality and the use of the LRINEC score is very helpful in decision making for health workers. CONCLUSION: The key to the management of NF is early diagnosis, debridement, removal of necrotic tissue, amputation, and use of empirical antibiotics.

Impact of COVID-19 Lockdown on the Metabolic Control Parameters in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Abrupt implementation of lockdowns during the coronavirus disease 2019 (COVID-19) pandemic affected the management of diabetes mellitus in patients worldwide. Limited access to health facilities and lifestyle changes potentially affected metabolic parameters in patients at risk. We conducted a meta-analysis to determine any differences in the control of metabolic parameters in patients with diabetes, before and during lockdown. METHODS: We performed searches of five databases. Meta-analyses were carried out using random- or fixed-effect approaches to glycaemic control parameters as the primary outcome: glycosylated hemoglobin (HbA1c), random blood glucose (RBG), fasting blood glucose (FBG), time-in-range (TIR), time-above-range (TAR), time-below-range (TBR). Mean difference (MD), confidence interval (CI), and P value were calculated. Lipid profile was a secondary outcome and is presented as a descriptive analysis. RESULTS: Twenty-one studies enrolling a total of 3,992 patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM) were included in the study. Patients with T1DM showed a significant improvement of TIR and TAR (MD=3.52% [95% CI, 0.29 to 6.74], I2=76%, P=0.03; MD=-3.36% [95% CI, -6.48 to -0.25], I2=75%, P=0.03), while FBG among patients with T2DM significantly worsened (MD=3.47 mg/dL [95% CI, 1.22 to 5.73], I2=0%, P<0.01). No significant difference was found in HbA1c, RBG, and TBR. Use of continuous glucose monitoring in T1DM facilitated good glycaemic control. Significant deterioration of lipid parameters during lockdown, particularly triglyceride, was observed. CONCLUSION: Implementation of lockdowns during the COVID-19 pandemic did not worsen glycaemic control in patients with diabetes. Other metabolic parameters improved during lockdown, though lipid parameters, particularly triglyceride, worsened.

Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study.

Introduction: Diabetes mellitus has been perceived as the worsening factor for coronavirus disease 2019 (COVID-19), where diabetes mellitus patients with pre-existing inflammatory condition could develop acute respiratory disease syndrome as well as multi-organ dysfunction. Managing diabetes mellitus amidst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also a matter of concern as several antidiabetic therapies could affect the progression of COVID-19. This study aimed to provide the clinical characteristics and outcomes of patients with both COVID-19 and diabetes mellitus receiving blood glucose lowering therapies and COVID-19 symptomatic treatments. Methods: This retrospective study was performed on 260 medical records of patients hospitalized between May 2020 to February 2021 in East Java, Indonesia. Patients were confirmed COVID-19 positive based on the results from real time polymerase chain reaction (RT-PCR) using nasal swab samples collected on hospital admission. Data included were demographic characteristics, COVID-19 symptoms, severity of COVID-19, comorbidities (other than diabetes mellitus), fasting blood glucose (FBG), and 2-hours post-prandial blood glucose (2hPBG), and outcomes. Results: Most of the patients had age range of 41-60 years old (76.1%) with more than a half of the subjects (60%) were obese. Patients with uncontrolled diabetes were distributed evenly among the COVID-19 severities (74.3% in asymptomatic group, 73.6% in mild group, and 74.1% in moderate group). There were reductions in FBG and 2hPBG levels measured before (210.75±81.38 and 271.19±100.7 mg/dL, respectively) and after the treatment (181.03±68.9 and 222.01±86.96 mg/dL, respectively). All patients received multivitamin and symptomatic treatment for COVID-19. Oral antidiabetic drug (57.6%) and insulin (28.8%) were administered to lower the blood glucose level of the patients. As many as 96.9% patients survived, while 3.1% died. Conclusion: COVID-19 could affect the blood glucose level, suggesting the importance of antihyperglycemic therapies among patients with both COVID-19 and diabetes mellitus.