Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 Concentrations between Normal and Prediabetic Subjects: A Crossover Study

Background. The extract of Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (sambiloto) (穿心蓮 chuān xīn lián) has been reported to have an antidiabetic effect on mice models and has been used traditionally in the community. The exact mechanism of sambiloto extract in decreasing plasma glucose is unclear, so we investigated the role of sambiloto extract in the incretin pathway in healthy and prediabetic subjects. Methods. This study was a randomized, placebo-controlled, crossover, double-blind trial. It included 38 people who were healthy and 35 people who had prediabetes. All subjects were randomly assigned to receive either the intervention sambiloto extract or a placebo. All subjects were randomly assigned to receive the first intervention for 14 days. There was a washout period between subsequent interventions. The primary outcome was glucagon-like peptide 1 (GLP-1) concentration, and secondary outcomes were fasting insulin, 2-hour postprandial insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose, 2-hour postprandial blood glucose, dipeptidyl peptidase-4 (DPP-4), and glycated albumin before and after the intervention. Result. After the intervention, GLP-1 concentration significantly increased in prediabetes by 19.6% compared to the placebo ( p = 0.043 ). There were no significant differences in the changes of fasting insulin, 2-hour postprandial insulin, HOMA-IR, fasting blood glucose, 2-hour postprandial blood glucose, DPP-4, and glycated albumin levels after the intervention. Sambiloto extract did not inhibit the DPP-4 enzyme in healthy and prediabetic subjects. Conclusion. Sambiloto extract increased GLP-1 concentration without inhibiting the DPP-4 enzyme in prediabetic subjects. This trial is registered with ClinicalTrials.gov (ID: NCT03455049), registered on 6 March 2018—retrospectively registered (https://clinicaltrials.gov/ct2/show/NCT03455049).

Significance of inflammatory biomarkers and urethral histology in patients with urethral stricture disease in relation to treatment outcome—a single centre prospective study in the north-eastern part of India

Background Inflammation plays a very important role in defining the urethral stricture. Inflammatory biomarkers may play an important role in predicting the underlying pathophysiology as well as outcome of surgery. Histology of urethral strictures along with histology of urethra proximal and distal to stricture segment may have a role in predicting the outcome of the surgery. The literature discussing this aspect is rare; thus, this novel study aimed to find out the role of inflammatory biomarkers and urethral histology in predicting the outcome of surgery in urethral stricture disease. Methods This prospective study had 105 patients with age more than 15 years with urethral stricture. Baseline characteristics, routine blood tests including inflammatory blood markers (CRP, ESR, HbA1C, fasting insulin, serum ferritin, etc.) were recorded. They underwent various types of surgery, and first biopsy was taken from stricture segment and second biopsy from proximal to stricture segment and third biopsy from distal to stricture segment and evaluated for the presence of features of lichen sclerosus and inflammation. Primary endpoint was to diagnose the role of inflammatory biomarkers and histology of stricture in stricture recurrence. Results Their mean age was 43.3 ± 13.46 years. Mean CRP of 11.54 ± 3.64 in patients with failure and 9.59 ± 2.77 in patients with successful outcome (p 0.025). Other inflammatory biomarkers like HbA1C, fasting insulin, ESR, serum ferritin, NLR had no significant correlation with the outcome. The presence of features of lichen sclerosus like hyperkeratosis and severe inflammation in stricture segment predicted higher likelihood of failure. Histology of proximal and distal segment of urethral stricture had no significant relationship in predicting outcome. Staged urethroplasty with buccal mucosal graft outperformed single-stage urethroplasty in biopsy-proven LS strictures. Conclusions The present study found a negative impact of increased CRP and the presence of features of lichen sclerosus in urethral histology with the outcome of urethral stricture disease. Thus, our study confirms that inflammatory biomarkers (CRP) and histology of stricture segment play a significant role predicting the outcome of surgery.

Associations between weight loss history and factors related to type 2 diabetes risk in the Stop Diabetes study

Background Frequent weight loss attempts are related to maladaptive eating behaviours and higher body mass index (BMI). We studied associations of several type 2 diabetes (T2D) risk factors with weight loss history, defined as the frequency of prior weight loss attempts, among Finnish adults at increased risk for T2D. Methods This study (n = 2684, 80% women) is a secondary analysis of the 1-year StopDia lifestyle intervention with digital intervention group, digital intervention + face-to-face counselling group, or control group. The frequency of prior weight loss attempts was categorized into five groups: no attempts/no attempts to lose weight, but trying to keep weight stable/1–2 attempts/3 or more attempts/ continuous attempts. Data on emotional eating and social/emotional nutrition self-efficacy were collected with a digital questionnaire. We assessed baseline differences between categories of weight loss history as well as the intervention effects. Results Altogether 84% of participants had attempted weight loss. Those with one or more weight loss attempts had higher BMI, larger waist circumference, and more emotional eating compared to ‘no attempts’ and ‘no attempts to lose weight, but trying to keep weight stable’ categories. The ‘no attempts’ category had the highest baseline fasting insulin, whereas it showed the largest decrease in this measure with the intervention. This change in fasting insulin in the ‘no attempts’ category was significantly different from all the other categories. Emotional nutrition self-efficacy slightly improved in the ‘no attempts’ category, which was significantly different from its concomitant decrease in the categories ‘1-2 attempts’ and ‘3 or more attempts’. The intervention group assignment did not affect the results. Conclusions Multiple attempts to lose weight may unfavourably affect T2D risk factors as well as lifestyle intervention outcomes. More research is needed on how weight loss frequency could affect T2D risk factors and how to design lifestyle interventions for individuals with frequent previous weight loss attempts.

Variability of glucose, insulin, and lipid disturbances in first-episode psychosis: a meta-analysis

Background First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation. Methods We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change. Results Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12–1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10–1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09–1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12–1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06–1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01–1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09–1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00–1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes. Conclusions Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.

Novel lipidomic signature associated with metabolic risk in women with and without polycystic ovary syndrome

Background Dyslipidaemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population. Objective Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS. Methods Using pre-existing data and bio-banked samples from 76 women (n=42 with PCOS), we profiled &gt;700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual X-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing. Results Despite finding no differences by PCOS status, lysophosphatidylinositol (LPI) species esterified with an 18:0 fatty acid were the strongest lipid species associated with all the metabolic risk factors measured in women with and without PCOS. Across the cohort, higher concentrations of LPI(18:0) and lower concentrations of lipids containing docosahexaenoic acid (DHA, 22:6) n-3 polyunsaturated fatty acids (PUFA) were associated with higher adiposity, insulin resistance, fasting insulin, HbA1c and FAI, and lower SHBG. Conclusions Our data indicate that a distinct lipidomic signature comprising high LPI(18:0) and low DHA-containing lipids are associated with key metabolic risk factors that cluster in PCOS, independent of PCOS status. Prospective studies are needed to corroborate these findings in larger cohorts of women with varying PCOS phenotypes.

Correlation of Vitamin D Levels with Polycystic Ovary Syndrome: A Cross-sectional Study

Objective: To compare vitamin D status in, women with PCOS & fertile women without PCOS and its subsequent evaluation. Introduction: PCOS is an endocrine disorder of women in reproductive age, characterised by obesity, hyperandrogenaemia and insulin resistance. Women with PCOS tend to be overweight and have increased risk of development of Type II Diabetes and cardiovascular disease. Exact Etiology of PCOS still remain an enigmatic dilemma however various studies conducted till date include diet and lifestyle modification as the key factor to promote health, BMI, reduced hyperinsulinemia and reduce the risk of development of PCOS. Main aim of our study was to compare vitamin D status in women having PCOS, with fertile women in a tertiary care hospital in Uttarakhand. Methodology: The conducted study was cross sectional, involving the enrolment of 100 women comprising of 50 women with PCOS and 50 fertile women without PCOS. Participants were selected from gynaecological OPD at Shri Mahant Indiresh Hospital, associated with Shri Guru Ram Rai Institute of Medical Sciences, Dehradun from July 2019 to January 2020. The diagnostic criteria of PCOS used was the Rotterdam criteria. The serum 25-hydroxy vitamin D and other metabolic markers were measured. Vitamin D deficiency was defined as serum 25 (OH) D concentrations less than 20 ng/ml measured on an instrument named as miniVidas (BioMerieux, Germany) based on ELFA (enzyme linked fluorescent assay). Results: Serum 25-hydroxyvitamin D was significantly lower in women with PCOS compared to fertile controls (p< 0.0001), and the prevalence rates of 25(OH) D deficiency and insufficiency were higher in women with PCOS than in fertile women (p < 0.0001). The study results showed that the prevalence of 25 (OH) D deficiencies in PCOS women was significantly high. Serum 25 (OH) D concentrations were significantly negatively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting insulin, total cholesterol and low-density lipoprotein cholesterol (LDL-C), (P < 0.05). In comparison, serum 25 (OH) D concentrations were significantly positively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Increased BMI and WHR, high levels of fasting insulin, total cholesterol and LDL-C were regarded as risk factors, but high level of HDL-C was considered to be protective factor of vitamin D deficiency in PCOS women. Conclusion: The study demonstrated that women with PCOS have a significantly lower 25(OH) D compared to fertile controls. A compromised vitamin D status in PCOS women is associated with a higher prevalence and metabolic risk of PCOS in women.

A Significance Assessment of Diabetes Diagnostic Biomarkers Using Machine Learning

Diabetes can be diagnosed by either Fasting Plasma Glucose or Hemoglobin A1c. The aim of our study was to explore the differences between the two criteria through the development of a machine learning based diabetes diagnostic algorithm and analysing the predictive contribution of each input biomarker. Our study concludes that fasting insulin is predictive of diabetes defined by FPG, but not by HbA1c. Besides, 28 other fasting blood biomarkers were not significant predictors of diabetes.

Frequency of Insulin Resistance in People with Thyroid Dysfunction

Background: Thyroid dysfunction is an endocrine disorder with a recognized association with type 2 diabetes mellitus. Thyroid hormones have a remarkable effect on glucose metabolism and can cause insulin resistance (IR). This study was aimed at assessing the relationship between IR and thyroid dysfunction. Methods: This case–control study was conducted at the endocrinology outpatient clinics of Ibrahim Malik Hospital and Omdurman Military Hospital in Khartoum State, Sudan between May 2018 and January 2019. Fasting blood glucose (FBG), fasting insulin level, and thyroid function test (TFT) were measured for each candidate and IR was estimated using the HOMA-IR equation. Results: Thirty-one patients with thyroid dysfunction and fifty-seven control participants were enrolled. The highest mean FBG was found among cases (105.3 ± 15.7 mg/dl) compared to the controls (97 ± 12.1 mg/dl), but the difference was not statistically significant (P-value = 0.598). The mean fasting insulin level was 9.22 ± 4 IU/ml in the cases and 9.4 ± 4.2 IU/ml in controls, without a significant difference (P-value = 0.681). The highest HOMA-IR score was found among cases (2.4 ± 1.2). It was 2.4 ± 1.3 in hyperthyroidism, 2.3 ± 1.1 in hypothyroidism, and 2.4 ± 1.2 in controls, and the difference was insignificant (P-value = 0.859). IR was higher in the cases (58.1%) compared to the controls (52.6%) but again not statistically significant (P-value = 0.396). Among cases, IR was encountered in 61.9% and 50% of hyperthyroid and hypothyroid patients, respectively. Conclusion: Patients with thyroid dysfunction have some level of IR that was not statistically significant when compared with controls.

Prevalence of Vitamin D Deficiency and Its Association with Insulin Resistance in Obese Women with Normal Fasting Glucose

Background and Objective. Association of vitamin D (25-hydroxyvitamin-D; 25(OH)D), with glucose metabolism is ethnic dependent. We study the relation of vitamin D and its metabolites with the glycemic profile of obese women. Patients and Methods. Informed consent and demographic information was collected from obese ( BMI ≥ 30 kg / m 2 ) and nonobese women. A blood sample in fasting was obtained and analyzed for fasting glucose, fasting insulin, serum 25(OH)D, serum parathyroid hormone (PTH), and calcium levels. Insulin resistance (IR), detected by Matthews’ method (1985), was considered in women with HOMA − IR ≥ 2.5 . Vitamin D concentrations < 12 ng / ml were considered vitamin D deficiency. Results. A total of 264 obese and 133 normal BMI women (controls) of age range 20-50 years were selected. Obese women had significantly lower vitamin D compared to control women ( P < 0.05 ). Among euglycemic ( fasting glucose < 100 mg / dl ) obese women ( n = 221 ), 90 (40.7%) were vitamin D deficient. Serum PTH and calcium levels were negatively correlated, though nonsignificantly with vitamin D ( r = − 0.172 , P = 0.090 , and r = − 0.051 , P = 0.557 , respectively). The mean age, BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), fasting glucose, fasting insulin, PTH, and calcium were not significantly different in vitamin D-deficient as compared to nondeficient obese women. IR was detected in 109 (49.3%) obese women. Mean HOMA-IR in vitamin D-deficient women was significantly higher than that in the nondeficient obese women ( 3.03 ± 1.64 vs. 2.40 ± 1.02 ; P = 0.041 ), but the percentage of women with IR was comparable in both groups (51.1% vs. 45.8%; P = 0.745 ). Univariate analysis revealed that HOMA-IR was negatively correlated with vitamin D and positively with BMI and PTH. A multivariate regression analysis, stepwise method revealed that BMI and PTH were independent determinants of HOMA-IR instead of vitamin D. Conclusion. More than 40% of obese women were vitamin D deficient. Among euglycemic obese women, 49% were insulin resistant. Prevalence of insulin resistance, though negatively correlated with vitamin D, could be better explained by BMI and PTH levels.