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

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

BACKGROUND: It is crucial to understand the seasonal variation of Metabolic Syndrome (MetS) for the detection and management of MetS. Previous studies have demonstrated the seasonal variations in MetS prevalence and its markers, but their methods are not robust. To clarify the concrete seasonal variations in the MetS prevalence and its markers, we utilized a powerful method called Seasonal Trend Decomposition Procedure based on LOESS (STL) and a big dataset of health checkups. METHODS: A total of 1,819,214 records of health checkups (759,839 records for men and 1,059,375 records for women) between April 2012 and December 2017 were included in this study. We examined the seasonal variations in the MetS prevalence and its markers using 5 years and 9 months health checkup data and STL analysis. MetS markers consisted of waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG). RESULTS: We found that the MetS prevalence was high in winter and somewhat high in August. Among men, MetS prevalence was 2.64 ± 0.42 (mean ± SD) % higher in the highest month (January) than in the lowest month (June). Among women, MetS prevalence was 0.53 ± 0.24% higher in the highest month (January) than in the lowest month (June). Additionally, SBP, DBP, and HDL-C exhibited simple variations, being higher in winter and lower in summer, while WC, TG, and FPG displayed more complex variations. CONCLUSIONS This finding, complex seasonal variations of MetS prevalence, WC, TG, and FPG, could not be derived from previous studies using just the mean values in spring, summer, autumn and winter or the cosinor analysis. More attention should be paid to factors affecting seasonal variations of central obesity, dyslipidemia and insulin resistance.
Male ; Female ; Humans ; Metabolic Syndrome/epidemiology* ; Seasons ; Prevalence ; Climate ; Insulin Resistance ; Triglycerides

Female ; Humans ; Hypoglycemic Agents/therapeutic use* ; Insulin Resistance ; Metformin/therapeutic use* ; Phosphatidate Phosphatase ; Pioglitazone/therapeutic use* ; Polycystic Ovary Syndrome/genetics*

Background: Acute coronary syndrome (ACS) is a major cardiovascular problem due to its high hospitalization and mortality rates. One of the risk factors for atherosclerosis that leads to ACS is insulin resistance (IR) which plays a role in the pathogenesis and development of cardiovascular events. This study aims to determine the relationship between IR and in-hospital outcomes in non-diabetic patients with ACS. Methodology: This was a cohort study conducted from January-June 2021. Insulin resistance was assessed using the Admission insulin resistance index (AIRI). This measurement was performed once during the patient's admission, and then the outcome was observed during hospitalization. The observed in-hospital outcomes were composite outcomes; namely, heart failure, arrhythmia, cardiogenic shock, and death. The statistical tests used were ANOVA, independent T and Chi-Square tests. Statistical test results were considered significant if p<0.05. Results: This study included 60 subjects (51 males and 9 females). Analysis revealed that AIRI was higher in patients with composite outcomes (mean 9.97 ± 4.08) than in patients without composite outcomes (mean 7.71 ± 4.06) (p<0.05); AIRI was higher in patients with heart failure (mean 10.72 ± 3.83) than in patients without heart failure (mean 7.25 ± 3.84) (p<0.001). Patients with IR had a higher rate of heart failure complications [OR 5.5 95% CI (1.56-19.38) (p=0.005)]. Conclusion There is an association between AIRI and composite outcomes. Patients with IR have 5.5 times the risk of developing heart failure.
insulin resistance ; acute coronary syndrome

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
Animals ; Female ; Humans ; Rats ; Cell Proliferation ; Curcumin/therapeutic use* ; Follicle Stimulating Hormone ; Glucose ; Hyperandrogenism ; Insulin Receptor Substrate Proteins/metabolism* ; Insulin Resistance ; Ovarian Cysts ; Ovarian Neoplasms ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Polycystic Ovary Syndrome/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Testosterone

Objective: To explore abdominal fat mass distribution and contents among obese children via magnetic resonance imaging (MRI), and analyze the correlations of abdominal adipose tissue with anthropometric and metabolic parameters. Methods: Cross-sectional study. There were 60 obese children admitted to the Children's Health Care Department and Endocrinology Department at Children's Hospital of Nanjing Medical University from July 2016 to December 2018. Children's gender, age, height, weight, body composition, waist circumference and blood pressure were recorded. The levels of fasting blood glucose, lipids, insulin were measured, and liver ultrasound was performed, and the body mass index Z score (BMI-Z), waist-to-height ratio (WHtR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. In addition, contents of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) were calculated according to feedback of abdominal MRI scan images. The associations between the contents of abdominal adipose tissue, physical examination status and metabolic disorders among obese children were analyzed through correlation analysis and regression analysis. Receiver operating characteristic (ROC) curve was used to compare the accuracy of fat mass in different parts of the abdomen in predicting their metabolic disorders. Results: A total of 60 children were enrolled in the study, included 44 boys and 16 girls, with age of (9.2±1.4) years. The contents of SAT, VAT and TAAT among the 60 children were positively associated with BMI-Z (r=0.60, 0.46, 0.59), body fat percentage (r=0.64, 0.67, 0.68) and waist-to-height ratio (r=0.60, 0.57, 0.61) (all P<0.01). Meanwhile, contents of SAT and TAAT were also positively correlated with systolic blood pressure (r=0.47, 0.49), triglyceride (r=0.33, 0.35) and HOMA-IR (r=0.33, 0.28)(all P<0.05). In order to adjust the confounding effects among various variables, regression analysis was applied and the result showed that the body fat percentage (β=0.59, 0.66, 0.65) and waist-to-height ratio (β=0.53, 0.63, 0.59) were most related to abdominal fat contents (all P<0.01), including SAT, VAT and TAAT among obese children. According to ROC, SAT had outstanding evaluation performances for the diagnosis of insulin resistance and metabolic syndrome, while VAT had excellent evaluation performances for non-alcoholic fatty liver disease (area under curve=0.68, 0.69, 0.69, 95%CI 0.54-0.82, 0.55-0.84, 0.53-0.85, P=0.017, 0.014, 0.019). Conclusions: As one of the best indexes, body fat percentage and WHtR can be used to predict the contents of SAT, VAT and TAAT among obese children. With the increase of abdominal SAT or VAT, the risks for insulin resistance, metabolic syndrome and non-alcoholic fatty liver disease would increase. Assessment of abdominal fat and metabolic risks in obese children should combine BMI-Z with waist circumference and body composition analysis.
Abdominal Fat/metabolism* ; Body Mass Index ; Child ; Cross-Sectional Studies ; Female ; Humans ; Insulin Resistance ; Magnetic Resonance Imaging ; Male ; Metabolic Diseases/metabolism* ; Metabolic Syndrome/metabolism* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/metabolism*

OBJECTIVE: To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared. RESULTS: Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased ( CONCLUSION Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.
Acupuncture Therapy ; Blood Glucose ; Female ; Glucose ; Glucose Intolerance/therapy* ; Humans ; Insulin ; Insulin Resistance ; Polycystic Ovary Syndrome/therapy*

OBJECTIVE: To explore the effect of electro-acupuncture (EA) on glucose and lipid metabolism in unmarried patients with polycystic ovary syndrome (PCOS). METHODS: Fifty-four PCOS patients were equally randomized into true acupuncture group and sham acupuncture group (control) for totally 16 weeks of treatment by random method with a computerized randomization program. Patients in true acupuncture group accepted traditional acupuncture methods with EA and two sets of acupoint groups were used alternatively. The first set consisted of Zhongji (CV 3), Qihai (CV 6), Guilai (ST 29), Sanyinjiao (SP 6), Yinlingquan (SP 9), Hegu (LI4) and Baihui (GV 20), and the second set consisted of Tianshu (ST 25), ST 29, CV 3, CV 6, SP 6, Taichong (LR 3), Neiguan (PC) 6 and GV 20. Patients in the sham acupuncture group accepted shallow acupuncture methods through EA without electricity at 4 non-meridian points in each shoulder and upper arm. Outcome measures included body mass index (BMI), waist-hip-ratio (WHR), oral glucose tolerance test (OGTT), insulin release test, glucose and lipid metabolism indicators such as total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, adiponectin, leptin, visfatin, resistin, and interleukin (IL-6). RESULTS: Twenty-six subjects in the true acupuncture group and 20 subjects in the sham group completed the clinical trial. After 16 weeks of treatment, no significant difference in the outcome measures were observed between the two groups (P>0.05). However, as compared with baseline data, a reduction in weight, BMI, hipline, WHR, fasting glucose, homeostatic model assessment of insulin sensitivity, visfatin and HDL-C, and an increase in resistin and IL-6 were observed in the true acupuncture group (P<0.05). In addition, a reduction in visfatin and an increase in TC were also observed in the sham group (P<0.05). CONCLUSIONS Acupuncture may have a beneficial effect in the treatment of PCOS by improving glucose and lipid metabolism. Moreover, the sham acupuncture may be not completely ineffective. Sham acupuncture may improve some of the aspects of the glucose and lipid metabolism of PCOS patients through a placebo effect. (Registration Nos. ChiCTR-TRC-12002529 and NCT01812161).
Acupuncture Therapy ; Female ; Glucose ; Humans ; Insulin Resistance ; Lipid Metabolism ; Polycystic Ovary Syndrome/therapy* ; Single Person

Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive aged women. It is associated with metabolic problems such as obesity, insulin resistance and dyslipidemia. Obesity in itself is associated with insulin resistance and dyslipidemia. However, it remains unclear whether lean and obese PCOS women share the same metabolic profiles. Objective: The aim of this study was to identify the prevalence of abnormal glucose metabolism and dyslipidemia across different categories of body mass index among women with PCOS Methods: A retrospective cross – sectional study included 160 PCOS patients covering the years 2015 to 2017 was performed. Fisher’s exact test, one-way analysis of variance using Fisher-Hayter multiple comparisons procedure and independent-test were used to compare the prevalence of disease among the different categories of body mass index (i.e. non-obese, overweight and obese). Results: Among obese patients, the prevalence of pre-diabetes was 39.33% (35/89) and Type II diabetes mellitus was 8.99% (8/89). Among overweight, pre-diabetes patients were at 16.67% (5/30), while diabetics were only 6.67% (2). Among the non-obese population, only 17.07% (7/41) were classified as pre-diabetics while only 2.44% (1/41) were considered diabetic. For the prevalence of dyslipidemia, overweight and obese patients had the most proportion of affected individuals, at 90% (27/30) and 87.64% (78/89), respectively. Conclusion Abnormal glucose metabolism and dyslipidemia are more prevalent among obese and overweight women compared to non-obese PCOS patients.
Polycystic Ovary Syndrome ; Body Mass Index ; Insulin Resistance ; Dyslipidemias