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

BACKGROUND AND OBJECTIVE

Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients.

METHODS

We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated.

RESULTS

The mean age at diagnosis was 36.76 ± 13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6% of patients achieved at least more than 50% reduction in their prolactin levels.

CONCLUSION

Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.

Human ; Prolactinoma ; Pituitary Neoplasms ; Prolactin

Background and Objective: Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients. Methods: We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated. Results: The mean age at diagnosis was 36.76 ±13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6 % of patients achieved at least more than 50% reduction in their prolactin levels. Conclusion Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.
Prolactinoma ; Pituitary Neoplasms ; Prolactin

Background: Sepsis is a life-threatening organ dysfunction in response to an infection, and immediate administration of the first antibiotic dose, along with other resuscitative efforts, improves patient outcomes. This paved the way for the development of evidence-based sepsis pathways in different health institutions. Objectives: This study aims to assess the process of initial antibiotic therapy, from the time the loading dose of antibiotic was ordered to the time it was administered, for adult patients with sepsis admitted at the Emergency Department (ED) of the University of the Philippines – Philippine General Hospital (UP-PGH). Methods: In phase 1 of the study, a review of medical records was done to identify all adult patients diagnosed with sepsis in the ED from February 1 to August 31, 2022. A variant of time-motion analysis was used wherein three points in the sepsis pathway were identified: the t ime of diagnosis of sepsis/first chart order of antibiotics (point A), the time the chart order was noted by the nurse-in-charge (point B), and the documented time of f irst dose administration (point C). The mean and median duration (in hours) were then computed between these points. As an additional aim, we briefly presented the outcome of the population used. In phase 2, individual interviews and focused group discussions were done, involving key medical personnel in the sepsis pathway: physicians, nurses, pharmacists, and utility personnel. The data transcribed from these interviews was analyzed through a thematic examination. Results: A total of 508 adult patients were diagnosed with sepsis on record review, 442 of whom met the inclusion criteria. The median time it took for the nursein-charge to acknowledge the antibiotic order (points A to B) is 0.73 hours (IQR 0.27-1.7). Meanwhile, the median time between acknowledgment of the order to administration of antibiotics is 1.94 hours (IQR 0.83-6.63). More importantly, the median time from diagnosis-to-first dose (points A to C) is 3.53 hours (IQR 1.59–7.96), while the corresponding mean duration is 5.72 hours. In all cases, 44.6% and 12.4% of loading doses were given within three hours and within one hour after diagnosis, respectively. The all-cause mortality of all qualified cases was 64.7%. A total of 28 key medical personnel were recruited for phase 2. Issues regarding governance, information systems, finances, service delivery, and human resources were identified. In particular, the electronic chart system, a more stable supply of antibiotics, and the new pharmacy at the ER helped facilitate antibiotic delivery. Lack of personnel, gaps in information, and repetitive paperwork were cited as areas for improvement in the existing system. Conclusion In more than half of the study population, the target time from diagnosis to loading dose of at least 1 hour was not reached. The significant delays in sepsis treatment call for system-wide improvements to hasten the process of antibiotic delivery and reduce the poor outcomes associated with sepsis.
Human ; sepsis

Papillary thyroid carcinoma is the most common well-differentiated thyroid malignancy accounting for more than 80 to 90% of all thyroid tumors. It has an overall excellent prognosis owing to advances in screening via imaging and ultrasound-guided fine-needle aspiration biopsy, which have facilitated early detection, diagnosis, and surgical treatment followed by adjuvant radioactive iodine therapy. Exceptionally rare cases of papillary thyroid tumors may present with enormous growth due to delayed consultation and, thus, late diagnosis, posing a challenge to definitive management, quality of life, overall survival, and prognosis. We report a case of a 35-year-old woman who presented with a 4-year history of a bleeding exophytic and fungating anterior neck mass. Computed tomography showed a fungating mass arising from the left thyroid lobe that measured 14.1 x 14.0 x 11.1 cm with areas of necrosis and hemorrhage, left internal jugular vein thrombus formation, and compression of the left internal carotid artery. The mass causes a displacement of the trachea to the right side and multiple bilateral cervical lymphadenopathies. The patient was fully aware, and she consented to undergo wide excision, total thyroidectomy, neck dissection, and pectoralis major muscle flap reconstruction. However, she went into arrest intraoperatively attributed to massive pulmonary embolism. Papillary thyroid cancer is well known for its excellent prognosis. However, outcomes may not be favorable and can even be fatal in advanced and extensive cases. Although fungating papillary cancers are rare, they remain more common in the developing countries, where early detection and access to healthcare remains limited. They also represent a big challenge to surgeons. Even if the outcome was not good, we opted to report this case as there were many learning points. If only patients with good and excellent outcomes are reported in the literature, it will overestimate the treatment success of these complex cases.
papillary thyroid cancer

Sheehan’s syndrome is characterized by hypopituitarism following ischemic necrosis of the pituitary gland caused by postpartum hemorrhage and impaired blood supply to the enlarged pituitary gland during pregnancy. The worldwide prevalence has since decreased due to improvements in obstetric care. Behavioral change is a rare presentation and is often misdiagnosed and managed as psychosis. We report a 42-year-old woman presenting with behavioral changes associated with postpartum failure of lactation and amenorrhea. Hormonal work-up revealed panhypopituitarism; serum cortisol, 98.93 (NV: 138–690 nmol/L); free T4, less than 5.15 (NV: 11.5–23.00 pmol/L); free T3, less than 2.30 (NV: 2.89–4.88 pmol/L); FSH, 3.63 (NV: 30–135 mIU/mL); LH, 3.88 (NV: 13–80 mIU/mL); serum estradiol, 3.89 (NV: 10.41–35.0 pg/mL); IGF-1, 13.13 (NV: 56–194 ng/mL); and serum prolactin, 1.8 (NV: 2.6–24.8 ng/mL). Cranial MRI with contrast revealed an atrophic pituitary gland consistent with Sheehan's syndrome. The symptoms improved substantially upon replacement with steroids and thyroid hormones and she was able to resume her routine activities. The psychiatric features of hypopituitarism can be attributed to a combination of hypothyroidism, hypoglycemia, and hypocortisolism and have been shown to reverse with adequate hormone replacement.
Hypopituitarism ; Psychotic Disorders ; Hypopituitarism

Diabetes mellitus (DM) is a known risk factor for morbidity and mortality among patients with COVID-19 based on recent studies. While there are many local and international guidelines on inpatient management of diabetes, the complicated pathology of the virus, the use of glucose-elevating drugs such as glucocorticoids, antivirals and even inotropes, and various other unique problems has made the management of in-hospital hyperglycemia among patients with COVID-19 much more difficult than in other infections. The objective of this guidance is to collate and integrate the best available evidence that has been published regarding in-patient management of diabetes among patients with COVID-19. A comprehensive review of literature was done and recommendations have been made through a consensus of expert endocrinologists from the University of the Philippines-Philippine General Hospital (UP-PGH) Division of Endocrinology, Diabetes and Metabolism. These recommendations are evolving as we continue to understand the pathology of the disease and how persons with diabetes are affected by this virus.
COVID-19 ; SARS-COV-2

Objectives: To evaluate the safety and efficacy of heparinoid supplementation on all-cause mortality and disease progression in diabetic kidney disease (DKD). Methodology: Trials evaluating heparinoid supplementation in DKD were included. Two authors performed a literature search with eligible studies undergoing validity screen, data extraction, and statistical analysis. Results were calculated using the Mantel-Haenszel odds ratio for dichotomous variables and the inverse variance method for continuous variables, and pooled using a random or fixed effects model depending on heterogeneity Results: Twelve trials were included in the analysis. Eight involved sulodexide while two each involved low molecular weight heparin and danaparoid. We found no statistically significant difference between the heparinoid and placebo groups for all-cause mortality (95% CI, HR 0.79 [0.41, 1.53], p=0.49), number of patients reaching therapeutic success (95% CI, OR 0.97 [0.71, 1.33], p=0.87), serum creatinine (95% CI, MD 2.55 umol/L [-0.54, 5.65], p=0.11), and creatinine clearance (95% CI, MD -8.55 mg/min [-18.28, 1.18], p=0.09). We also found no statistically significant difference in urinary albumin excretion rate (UAER) between Type 2 heparinoid-treated DKD patients compared to placebo (95% CI, log transformed MD 0.13 mg/24h [-0.42, 0.68], p=0.65); however, a statistically significant UAER reduction was seen in Type 1 heparinoid-treated DKD patients compared to placebo (95% CI, log-transformed MD -1.5 mg/24h [-2.79, -0.21], p=0.02). This subgroup analysis was performed due to initial heterogeneity (I^2=57%). Conclusion Heparinoid supplementation was not associated with statistically significant changes in Type 2 DM patients. However, it may be associated with a statistically significant UAER reduction of approximately 31.62 mg/24 h as compared to placebo in Type 1 DM patients. Due to sparse data on hard clinical outcomes, larger studies are recommended.
Diabetes Mellitus ; Diabetic Nephropathies ; Heparinoids ; Meta-Analysis

Introduction: Hazards of hypoglycemia include accidents, cardiovascular events, neurologic damage, and impaired hypoglycemia awareness (IHA) which presents as inability to perceive and respond to hypoglycemic warning symptoms. Objective: This study aimed to develop the first questionnaire evaluating IHA adapted from Clarke Hypoglycemia Index (CHI) and validated among adult Filipino patients with Type 2 Diabetes Mellitus (T2DM). Methodology: A questionnaire development study was conducted involving CHI linguistic translation, its modification through literature review and focus group discussions, panel synthesis, and content validity. A cross-sectional analytic study followed by administration of the questionnaire to 117 adult Filipinos with T2DM, advanced age, long-standing T2DM, insulin or sulfonylurea, polypharmacy, comorbidities and/or prior hypoglycemia. There were 9 participants in pilot testing, 69 in criterion validity against continuous glucose monitoring (CGM), and 108 in construct validity. Results: IHA domains in the concept map included Elusive Euglycemia Model, Developmental Model, and Cognitive Model. The Filipino-CHI formulated had 8 questions with content validity scores ranging from 87.5-93.75%. Owing to brevity, its internal consistency Cronbach’s alpha was 0.45. Criterion validity against CGM yielded 21 patients with biochemical hypoglycemic events, of which 2 had clinical hypoglycemic events and 19 were positive monitor-identified IHA. A questionnaire IHA cutoff score of ≥4 had sensitivity of 89.47%, and area under the curve of 0.55. Conclusion An 8-item questionnaire evaluating IHA among adult Filipino T2DM patients was developed and validated.
Diabetes Mellitus ; Hypoglycemia ; Surveys and Questionnaires

Objectives: To evaluate the safety and efficacy of heparinoid supplementation on all-cause mortality and disease progression in diabetic kidney disease (DKD). Methodology: Trials evaluating heparinoid supplementation in DKD were included. Two authors performed a literature search with eligible studies undergoing validity screen, data extraction, and statistical analysis. Results were calculated using the Mantel-Haenszel odds ratio for dichotomous variables and the inverse variance method for continuous variables, and pooled using a random or fixed effects model depending on heterogeneity Results: Twelve trials were included in the analysis. Eight involved sulodexide while two each involved low molecular weight heparin and danaparoid. We found no statistically significant difference between the heparinoid and placebo groups for all-cause mortality (95% CI, HR 0.79 [0.41, 1.53], p=0.49), number of patients reaching therapeutic success (95% CI, OR 0.97 [0.71, 1.33], p=0.87), serum creatinine (95% CI, MD 2.55 umol/L [-0.54, 5.65], p=0.11), and creatinine clearance (95% CI, MD -8.55 mg/min [-18.28, 1.18], p=0.09). We also found no statistically significant difference in urinary albumin excretion rate (UAER) between Type 2 heparinoid-treated DKD patients compared to placebo (95% CI, log transformed MD 0.13 mg/24h [-0.42, 0.68], p=0.65); however, a statistically significant UAER reduction was seen in Type 1 heparinoid-treated DKD patients compared to placebo (95% CI, log-transformed MD -1.5 mg/24h [-2.79, -0.21], p=0.02). This subgroup analysis was performed due to initial heterogeneity (I^2=57%). Conclusion Heparinoid supplementation was not associated with statistically significant changes in Type 2 DM patients. However, it may be associated with a statistically significant UAER reduction of approximately 31.62 mg/24 h as compared to placebo in Type 1 DM patients. Due to sparse data on hard clinical outcomes, larger studies are recommended.
Diabetes Mellitus ; Diabetic Nephropathies ; Heparinoids ; Meta-Analysis