Hyperinsulinemia: an early biomarker of metabolic dysfunction.

Introduction: Hyperinsulinemia in the absence of impaired glucose tolerance and normal HbA1c is considered indicative of pre-diabetes. Very few Indian studies have focused on hyperinsulinemia particularly in young adults. The present study aimed to determine whether hyperinsulinemia may be present despite HbA1c being normal. Methods: This was a cross-sectional study conducted on adolescents and young adults aged 16-25 years living in Mumbai, India. The participants attended various academic institutions and were those who underwent screening as the first step of a clinical trial for studying the efficacy of almond intake in prediabetes. Results: Among this young population (n=1313), 4.2% (n=55) of the participants were found to be prediabetic (ADA criteria) and 19.7% of them had HbA1c levels between 5.7%-6.4%. However, almost, 30.5% had hyperinsulinemia inspite of normal blood glucose levels and normal HbA1c. Among those with HbA1c<5.7 (n=533), 10.5% (n=56) participants had fasting insulin>15 mIU/L and a higher percentage (39.4%, n=260) had stimulated insulin above 80 mIU/L. These participants had higher mean anthropometric markers than those with normal fasting and/or stimulated insulin. Conclusion: Hyperinsulinaemia in the absence of impaired glucose tolerance and normal HbA1c may provide a much earlier indicator of detection for risk of metabolic disease and progression to metabolic syndrome and diabetes mellitus.

Effect of Almond Consumption on Metabolic Risk Factors-Glucose Metabolism, Hyperinsulinemia, Selected Markers of Inflammation: A Randomized Controlled Trial in Adolescents and Young Adults.

A large percentage of the Indian population has diabetes or is at risk of pre-diabetes. Almond consumption has shown benefits on cardiometabolic risk factors in adults. This study explored the effect of almond consumption on determinants of metabolic dysfunction-blood glucose, lipids, insulin and selected inflammatory markers in adolescents and young adults aged 16-25 years from Mumbai city. This randomized controlled trial was conducted for a period of 90 days on individuals with impaired levels of fasting glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) and 2-h post-glucose value 140-199 mg/dL (7.8-11.0 mmol/L) and/or fasting insulin (≥15 mIU/ml)/stimulated insulin (≥80 mIU/ml). Of 1,313 individuals screened, 421 met the inclusion criteria, of which 275 consented to participate and 219 completed the trial. The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2018/02/011927. The almonds group (n = 107) consumed 56 g almonds daily, the control group (n = 112) was provided an iso-caloric cereal-pulse based snack. At baseline and endline, blood glucose, insulin, HbA1c, LDL-c, HDL-c, total and ox-cholesterol, triglycerides, hs-CRP, IL-6, TNF-α, adiponectin, leptin were measured and HOMA-IR and FG:FI ratios were calculated. Dietary intakes were assessed. The anthropometric measurements, biochemical markers as well as macronutrient intakes did not differ significantly between the two groups at baseline. Almond consumption significantly decreased HbA1c, total cholesterol and LDL-c. Stimulated insulin decreased post-intervention in both groups, but the decrease was greater in the almonds group. Fasting glucose was reduced post intervention in the controls with no change in the almonds group. FG:FI ratio decreased in the almonds group. TNF-α and IL-6 decreased in the almonds group, while it increased in the control group. Our results showed that almonds reduced HbA1c, LDL-c and total cholesterol levels in just 12 weeks of consumption in these adolescents and young adults who were at risk for developing diabetes. Almonds can be considered as part of food-based strategies for preventing pre-diabetes. Clinical Trial Registration: ClinicalTrials.gov, identifier: CTRI/2018/02/011927.

A Clinical Study of a Standardized Extract of Leaves of Dalbergia sissoo (Roxb ex DC) in Postmenopausal Osteoporosis.

CONTEXT: Dalbergia sissoo had shown anti-osteoporotic and fracture-healing activities in animal models of postmenopausal osteoporosis (PMO). Standardized extract of leaves of D. sissoo (SEL-Ds) was clinically evaluated for osteoporosis. AIMS: To investigate the anti-osteoporotic activity of D. sissoo in PMO by dual-energy X-ray absorptiometry (DXA), biochemical markers, and effect on clinical profile. Tolerability was assessed by organ function tests and adverse events. SETTINGS AND DESIGN: An open-labeled prospective clinical study in ambulant settings was conducted at the menopausal health-care facility of a women's hospital. MATERIALS AND METHODS: Thirty women (45-69 years) were enrolled for this 1-year study. Evaluations were basally, fortnightly twice, and three monthly four times. SEL-Ds (300 mg) twice daily was administered orally. Calcium (250 mg) and Vitamin D (200 IU) were given twice a day. The efficacy of SEL-Ds was assessed by DXA-scan (spine, femur), by biochemical markers, alkaline phosphatase (ALP), tumor necrosis factor-alpha (TNF-α), and anti-inflammatory marker high-sensitivity C-reactive protein (hs-CRP). Baseline symptom changes and adverse events were carefully recorded. STATISTICAL ANALYSIS: Summary statistics (n, mean, standard deviation, median, and maximum and minimum values) of changes from baseline values and Student's "t-" test for P values were used. RESULTS AND DISCUSSION: SEL-Ds was well tolerated at given dose for 1 year. Anti-osteoporotic and anti-inflammatory activities of SEL-Ds were demonstrated by reduction in TNF-α (12.04 ± 2.81-2.35 ± 1.08 pg/ml), ALP (208.75 ± 45.88-154.52 ± 37.25 IU/L), and hs-CRP (6.1 ± 0.77-3.9 ± 0.47 mg/L). BMD-score on DXA-scan also remained unchanged at majority of the bone locations (increased 13/75, unchanged 51/75, and decreased 08/75). CONCLUSIONS: D. sissoo has demonstrated anti-osteoporotic and anti-inflammatory activities as indicated by decline in circulating TNF-α along with concurrent reduction in ALP. The nondecline in BMD index in the majority confirms the anti-osteoporotic activity.

Role of cytokines in genesis, progression and prognosis of cervical cancer.

Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

Menopause and metabolic syndrome: A study of 498 urban women from western India.

INTRODUCTION: Metabolic syndrome (MS) is a cluster of risk factors for future development of type 2 diabetes mellitus and cardiovascular diseases. Menopausal transition with its incidental hormonal changes is considered to contribute to the development of MS. However, age is known to influence MS risk factors. OBJECTIVE: The present study explores the prevalence of MS in pre- and postmenopausal women from western India. METHODS: Four hundred and ninety eight women above 35 years of age, participating in women's health care program were assessed for the prevalence of MS using two criteria- International Diabetes Federation criteria (IDF) and Harmonization (H_MS) criteria. RESULTS: Prevalence of MS amongst postmenopausal women was significantly higher (P < 0.001) than that in premenopausal women by both, IDF (premenopausal 45% and postmenopausal 55%) and H_MS criteria (premenopausal 44% and postmenopausal 56%). However, this significance disappeared when data was adjusted for the confounding variable of age.

Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain.

We have examined the influence of thyroid hormone on adult hippocampal neurogenesis, which encompasses the proliferation, survival and differentiation of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we demonstrate that adult-onset hypothyroidism significantly decreases hippocampal neurogenesis. This decline is predominantly the consequence of a significant decrease in the survival and neuronal differentiation of BrdU-positive cells. Both the decreased survival and neuronal differentiation of hippocampal progenitors could be rescued by restored euthyroid status. Adult-onset hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the effects of thyroid hormone may be optimally permissive at euthyroid levels. Our in vivo and in vitro results revealed that adult hippocampal progenitors express thyroid receptor isoforms. The in vitro studies demonstrate that adult hippocampal progenitors exhibit enhanced proliferation, survival and glial differentiation in response to thyroid hormone. These results support a role for thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the possibility that altered neurogenesis may contribute to the cognitive and behavioral deficits associated with adult-onset hypothyroidism.