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

Abstract Introduction: Type 2 diabetes mellitus (T2DM) is a major global health concern characterized by insulin resistance, hyperglycemia, and chronic inflammation. Interest in natural adjunctive therapies has increased, particularly in mangosteen (Garcinia mangostana), which contains xanthone compounds in the peel with potential antidiabetic properties. Methods: This systematic review followed PRISMA 2020 guidelines. Literature searches were conducted using PubMed, Google Scholar, and ClinicalKey up to December 2022 for studies assessing mangosteen peel extract (MPE) or α-mangostin in diabetic human subjects. Eligible studies included randomized controlled and quasi-experimental trials reporting glycemic or metabolic outcomes. Risk of bias was evaluated using the Cochrane RoB tool. The primary result of this study is to evaluate the effects of mangosteen peel extract supplementation on key glycemic outcomes in patients with T2DM, specifically fasting blood glucose (FBG), HOMA-IR, and HbA1c. Results: A total of two studies (n=2) met the inclusion criteria. A randomized controlled pilot trial reported significant improvement in insulin sensitivity (HOMA-IR −53.2% vs −15.2%; p = 0.004) after 26 weeks of standardized mangosteen extract. A small quasi-experimental study reported a significant reduction in FBG following 7 days of mangosteen peel decoction. Discussion: Limited clinical evidence indicates that mangosteen peel extract may improve insulin sensitivity and lower fasting glucose in T2DM. However, the conclusions are limited by the small number of available studies, the short follow-up duration in one trial, and variability in extract preparation. Conclusion: Mangosteen peel extract demonstrates promising glycemic benefits, including improved insulin sensitivity and reduced fasting glucose. However, the available evidence remains limited by small sample sizes, short follow-up periods, and heterogeneity in extract formulations. Larger randomized controlled trials using standardized preparations are required before clinical recommendations can be made.
Garcinia mangostana ; mangosteen peel extract ; &alpha ; -mangostin ; type 2 diabetes mellitus ; insulin resistance ; oxidative stress

Introduction: Insulin resistance and progressive beta-cell dysfunction are key components of the pathophysiology of type 2 diabetes mellitus (T2DM). The triglyceride-to-highdensity lipoprotein cholesterol (TG/HDL) ratio has been widely used as a marker of insulin resistance. In addition, testosterone deficiency has been associated with adverse metabolic profiles and T2DM. However, the relationship between testosterone levels, insulin resistance, and betacell function in patients with T2DM remains incompletely understood. Methodology: A cross-sectional study was conducted involving 25 male patients with T2DM attending the diabetic clinic at Dr. Mohammad Hoesin General Hospital. Serum testosterone, C-peptide, TG, and HDL levels were obtained from routine clinical data. The TG/HDL ratio was calculated as an index of insulin resistance. Normality was assessed using the Shapiro–Wilk test, and due to the non-normal distribution of key variables, Spearman correlation analysis was applied. Results: A strong inverse correlation was observed between testosterone levels and TG/HDL ratio (r = -0.860, p <0.001), indicating that higher insulin resistance was associated with lower testosterone levels. In addition, TG/HDL ratio showed a strong negative correlation with C-peptide levels (r = -0.741, p <0.001), suggesting reduced beta-cell function in the presence of increased insulin resistance. Conclusion In patients with T2DM, increased insulin resistance is strongly associated with lower testosterone levels and reduced beta-cell function. These findings highlight the interaction between metabolic dysfunction and hormonal status in middle-aged and elderly patients with T2DM
Diabetes Mellitus, Type 2 ; Insulin Resistance ; Testosterone

Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by tumor secretion of insulin-like growth factor-2 (IGF-2), leading to recurrent hypoinsulinemic hypoglycemia. It is most commonly associated with large mesenchymal tumors, such as solitary fibrous tumor, particularly those arising from the pleura or lungs. This phenomenon, also known as Doege–Potter syndrome, may precede tumor detection or signal tumor recurrence. We report a striking case of late malignant recurrence presenting solely with hypoglycemia after a decade of remission. Case: A 68-year-old female was initially presented in 2016 with respiratory symptoms and recurrent symptomatic fasting and post-prandial hypoglycemia, and was found to have a large left upper lobe mass. Tumor resection in 2017 resulted in complete resolution of hypoglycemia. She remained asymptomatic for several years. In 2023, she developed recurrent hypoglycemia without respiratory or constitutional symptoms. Biochemical evaluation demonstrated hypoinsulinemic hypoglycemia with suppressed insulin and C-peptide, low IGF-1, and markedly elevated IGF-2, resulting in an IGF-2:IGF-1 ratio of 25, consistent with IGF-2-mediated NICTH. Computed tomography imaging revealed a large left thoracic mass with invasion into the intercostal muscles and diaphragm with extension toward the stomach, associated with contralateral lung nodules and possible liver metastases, suggesting recurrent malignant disease. Hypoglycemia improved with glucocorticoid therapy, and the patient was referred for oncological assessment. Despite initiation of systemic chemotherapy, her disease progressed and she succumbed during treatment. Conclusion This case highlights several important lessons: Firstly, recurrent hypoinsulinemic hypoglycemia warrants evaluation for NICTH even in the absence of tumor-related symptoms. Secondly, solitary fibrous tumors may recur or undergo malignant transformation after prolonged disease-free intervals; and glucocorticoids provide effective metabolic control but do not alter oncologic prognosis. Long-term surveillance should be considered in patients with prior solitary fibrous tumors due to the risk of delayed recurrence and paraneoplastic complications.
Insulin-Like Growth Factor II ; Hypoglycemia ; Neoplasms

Introduction: Acromegaly is an endocrine disorder caused by excess growth hormone (GH), causing somatic overgrowth, multiple comorbidities, and premature mortality. It is confirmed biochemically by an elevated GH level, which is not suppressed post oral glucose tolerance test (OGTT). The serum level of insulin-like growth factor-1 (IGF-1) is recommended for diagnosis, monitoring, and screening, and a normal level effectively excludes the disease. We report a patient with acromegaly who presented with normal IGF-1. Case: A 21-year-old female, with no known medical illness, presented with a persistent, progressive headache and amenorrhea for the past 6 months. She also noticed a change in facial appearance and an increase in the size of her hands and feet. Blood parameters revealed raised GH level of >50 ng/mL, normal IGF-1 30.3 nmol/L (12.17–44.80), mildly raised prolactin 692 mIU/L, low am cortisol 62 nmol/L (166–507), thyroid-stimulating hormone of 0.63 mIU/L (0.27–4.20), free thyroxine 4 11 pmol/L (12–22), low follicle-stimulating hormone 0.90 IU/L, luteinizing hormone <0.30 IU/L, estradiol <18.4 pmol/L, and fasting blood sugar of 17.7 mmol/L with hemoglobin A1c 9%. In view of normal IGF-1 with a high index of suspicion for acromegaly, she underwent OGTT which showed unsuppressed GH. Magnetic resonance imaging pituitary showed sellar mass 2.4 × 2.9 × 2.1 cm with suprasellar extension as well as extension into the right cavernous sinus, suggestive of pituitary macroadenoma. She was diagnosed with acromegaly with secondary adrenal insufficiency and central hypothyroidism with hypogonadotropic hypogonadism, complicated with poorly controlled diabetes. She was started on thyroxine and hydrocortisone replacement and required basal bolus insulin of 1.3 u/kg/day. Repeated IGF-1 showed a raised value, 85.4 nmol/L, after optimization of diabetes. She underwent endoscopic transsphenoidal surgery with normalization of blood sugar post-surgery. Blood pressure was normal throughout. Conclusion False negative or normal IGF-1 levels may result in patients with hepatic or renal failure, hypothyroidism, malnutrition, use of oral estrogen, severe infection, and poorly controlled diabetes mellitus. Hence, a low or normal IGF1 does not exclude acromegaly in patients with a high index of suspicion and warrants further investigation.
Acromegaly ; Insulin-Like Growth Factor I

Introduction: Acromegaly is usually diagnosed by elevated age- and sex-adjusted insulin-like growth factor-1 (IGF-1) levels reflecting chronic growth hormone (GH) excess. IGF-1 is preferred as a screening biomarker due to its longer half-life and reduced pulsatility compared with GH. However, IGF1 levels may be disproportionately low or only modestly elevated in certain clinical contexts, leading to diagnostic uncertainty. Pituitary apoplexy is one such condition in which acute tumor hemorrhage or infarction may disrupt sustained GH secretion and attenuate IGF-1 production Case: A 48-year-old female with hypertension, type 2 diabetes mellitus, and dyslipidemia presented with a 2-day history of severe headache, vomiting, and visual disturbance, on a background of progressive acral enlargement over 2 years. Examination revealed coarse facial features, prognathism, enlarged hands, and cranial nerve involvement. Magnetic resonance imaging demonstrated an invasive sellar– suprasellar pituitary macroadenoma with optic chiasmal compression and cavernous sinus encasement. Intravenous dexamethasone was initiated pre-operatively due to a significant mass effect. Biochemical evaluation showed markedly elevated random GH levels (>50 ng/mL) with only mildly elevated IGF-1 at 1.19 times the upper limit of normal, below the threshold at which confirmatory oral glucose tolerance testing may be omitted according to current guidelines. Other pituitary axes suggested evolving hypopituitarism. During admission, she developed severe hyperglycemia with marked insulin resistance, requiring high-dose insulin therapy (approximately 1.5 U/kg/day). She underwent urgent transsphenoidal surgery, with histopathology confirming a pituitary neuroendocrine tumor with extensive hemorrhage and infarction, consistent with pituitary apoplexy. Postoperatively, GH levels were suppressed to <5 ng/mL, insulin requirements decreased markedly, and hormone replacement was initiated for secondary adrenal insufficiency and central hypothyroidism. Conclusion This case highlights that IGF-1 levels below conventional diagnostic thresholds do not exclude clinically significant acromegaly, particularly in the setting of pituitary apoplexy. Integration of clinical phenotype, GH levels, and imaging findings is essential to avoid diagnostic delay and ensure timely management.
Acromegaly ; Insulin Resistance ; Pituitary Apoplexy

BACKGROUND

There is an increasing population of elderly patients with diabetes. Malnutrition has been associated to higher morbidity and mortality among these patients. Currently, there are limited data on malnutrition and its risk factors among elderly patients with diabetes in the Philippines.

OBJECTIVES

This study determined the prevalence, clinical profile and risk factors associated with malnutrition and identify the association of malnutrition with glycemic status and insulin resistance among elderly patients with diabetes.

METHODOLOGY

This is a cross-sectional study involving 117 elderly patients with diabetes seen at a tertiary hospital in Manila, Philippines. Demographic, anthropometric, and clinical data were collected. Mini-Nutritional Assessment-Short form (MNA-SF), Simple FRAIL questionnaire and Mini-cog assessment were administered. Patients were categorized into normal, at risk for malnutrition, and malnourished using the MNA-SF. Comparative and logistic regression analyses were performed to identify the clinical profile and possible risk factors.

RESULTS

The prevalence of malnutrition was 1.71% with 29.06% at risk for malnutrition. There was no significant difference in demographic, anthropometric and biochemical parameters between the different nutrition statuses. High BMI, central obesity, and increased insulin resistance were observed across all nutrition status. Frail patients had almost five times increased likelihood (OR=4.94, p=0.043) of developing malnutrition. Good glycemic control had two-fold decreased likelihood (OR=0.44, p=0.050) of malnutrition. Insulin resistance was not associated with malnutrition.

CONCLUSION

Malnutrition is prevalent among elderly patients with diabetes. Frailty and poor glycemic control increased the risk of malnutrition. Therefore, malnutrition screening should be routinely performed among these patients. Diabetes management among elderly patients should include maintaining good glycemic control and preventing frailty and its complications.

Human ; Malnutrition ; Diabetes Mellitus ; Glycemic Control ; Insulin Resistance

BACKGROUND

Diabetes is a chronic metabolic condition that represents a major public health issue worldwide, with Type 2 diabetes comprising 80-90% of all cases1. It is estimated that individuals with diabetes will increase from 451 million in 2021 to 693 million by 2045, with around 4.3 million individuals affected in the Philippines as of 20212,3,4. While insulin therapy is vital for managing diabetes, acceptance among patients is frequently obstructed by concerns about side effects, potential disruptions to their lifestyle, and stigma associated with injections.

OBJECTIVE

The objective of the study was to determine the barriers to insulin therapy among adult patients with Type 2 Diabetes mellitus of the Department of Family and Community Medicine of Quezon City General Hospital.

METHODS

This is a cross-sectional study carried out between July and September 2024 involving 117 participants with Type 2 diabetes. Information was gathered through self-administered questionnaires consisting of the Insulin Treatment Appraisal Scale (ITAS) and the SCREEM-RES questionnaire.

RESULTS

Majority of the participants (67.06%) were aged between 60 and 65, predominantly female (56%) and unemployed with a monthly family household income of less than 8,000 pesos. ITAS revealed negative perceptions towards insulin treatment, primarily due to fear and perceived loss of control. Family resources among the participants was revealed to be inadequate, as reflected in the SCREEM-RES questionnaire.

CONCLUSION

Age, education, employment status, household income, high negative attitude towards insulin and inadequate family resources are found to be barriers to initiating insulin. The study highlights the need for improved education to foster a supportive environment for insulin use and emphasizes the importance of involving patients in their treatment decisions for effective diabetes management and better long-term health outcomes.

Human ; Diabetes Mellitus, Type 2 ; Insulin ; Fear

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

OBJECTIVE: To investigate the effect of moxibustion on central insulin resistance related proteins of the rats suffering from diabetic cognitive decline, and analyze the underlying mechanism of moxibustion for cognition improvement. METHODS: Using the intraperitoneal injection of STZ combined with a high-fat diet, the rat model of diabetic cognitive decline were prepared. Twenty successfully-modeled rats were assigned randomly into a model group and a moxibustion group, 10 rats in each one. Besides, a blank group was set up with 10 rats collected. In the moxibustion group, suspending moxibustion was applied to "Baihui" (GV20), "Shenting" (GV24) and "Dazhui" (GV14) at the same time, 20 min in each intervention, once a day, and 6 interventions were delivered weekly and the duration of treatment was consecutive 4 weeks. The random blood glucose was measured using glucometer, and the learning-memory ability was detected by water maze test. HE staining was used to observe the morphology of neurons in the hippocampal tissue, real-time PCR assay was to detect mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in the hippocampal tissue. The Western blot method was employed to detect the protein expression of IRS1, PI3K, AKT, phosphorylated IRS1 (p-IRS1), phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the hippocampal tissue, and the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was calculated separately. The immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT was measured using immunofluorescence. RESULTS: Compared with the blank group, the rats of the model group exhibited higher random blood glucose (P<0.001), longer escape latency (P<0.001), severe pathological damage in the hippocampus, lower mRNA expression of IRS1, PI3K, and AKT (P<0.001), reduced ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT (P<0.001), and declined immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue (P<0.001). In comparison with the model group, for the rats of the moxibustion group, the random blood glucose decreased (P<0.05), the escape latency was shortened (P<0.01), the hippocampal pathological damage was attenuated, the mRNA expression of IRS1, PI3K and AKT increased (P<0.01), the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was elevated (P<0.01, P<0.05), and the immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue was strengthened (P<0.01, P<0.05). CONCLUSION In diabetic rats experiencing cognitive decline, moxibustion can enhance the learning-memory ability, which may be attributed to modulating the protein expression of IRS1, PI3K, and AKT, and their phosphorylation, activating insulin signal transduction, and reducing central insulin resistance.
Animals ; Moxibustion ; Insulin Resistance ; Rats ; Male ; Insulin Receptor Substrate Proteins/genetics* ; Rats, Sprague-Dawley ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cognitive Dysfunction/genetics* ; Diabetes Mellitus, Experimental/therapy* ; Hippocampus/metabolism* ; Acupuncture Points ; Phosphatidylinositol 3-Kinases/genetics*