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Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce.Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose.Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P =.001), in T2DM (2.87 to 4.62, P .001), and in controls (3.91 to 6.13, P .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls.In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.背景: 评价纤维结石性胰腺糖尿病(FCPD)内分泌和外分泌功能的研究很少。 方法: 测定FCPD组(n=20)、2型糖尿病(T2 DM)组(n=20)和对照组(n=20)空腹和75g葡萄糖后60min的胰岛素、C肽、胰高血糖素、肠泌素(胰高血糖素样肽1[GLP-1]和胃抑制肽[GIP])、二肽基肽酶IV(DPP-IV)水平。 结果: FCPD组空腹和糖负荷后C肽、胰岛素水平均低于T2 DM组和对照组。对照组糖负荷后胰高血糖素(pmol/L)降低(3.72; 2.29); T2 DM组升高(4.01; 5.73); FCPD组(3.44; 3.44)无明显变化。FCPD组(6.14~9.72; P=0.001)、T2 DM组(2.87~4.62; P0.001)和对照组(3.91~6.13; P0.001)糖负荷后活性GLP-1(pmol/L)升高。FCPD组空腹和糖负荷后GLP-1(pmol/L)活性中位数(6.14; 9.72)是T2 DM组(2.87; 4.62)的两倍; 是对照组(3.91; 6.13)的1.5倍(P0.001)。糖负荷后GIP(pmol/L)在所有组别中都升高:FCPD(15.83~94.14)、T2DM(21.85~88.29)、对照组(13.00~74.65), P0.01。不同组间GIP差异无统计学意义。对照组(1578.54,3012.00)和FCPD组(1609.95,1995.42)的DPP-IV浓度(ng/mL)升高; 而T2 DM组(1204.50,1939.50)的DPP-IV浓度无明显变化(P=0.131)。DPP-IV于三组间差异无统计学意义。FCPD组中粪弹性蛋白酶低于T2 DM组对照组。 结论: FCPD患者糖负荷后基础C肽和胰高血糖素降低; 在糖负荷后胰高血糖素不升高。FCPD的GLP-1; 而不是GIP; 与T2 DM和对照组(空腹和糖负荷后)相比升高了1.5-2倍; 而DPP-IV没有差异.

Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 acts primarily through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

Objective: Type 2 diabetes mellitus and thyroid dysfunction (TD) are two major public health endocrine problem, but the prevalence of TD and iodine status in patients with T2 DM in India is less studied. The study objective was to explore the prevalence of TD and to evaluate iodine health in type 2 diabetes patients attending a tertiary care center in Eastern India. Methods: Consecutive 100 patients with diabetes attending outpatient department were evaluated clinically and biochemically (thyrotropin [TSH], free thyroxine, anti-TPO antibody, and urinary iodine). We excluded pregnant women or patients taking drugs that can alter thyroid function. Subclinical hypothyroid and overt hypothyroidism were diagnosed as per standard definitions. Results: Out of 100 patients were analyzed, 51 (51%) were male. Mean (±standard deviation) age was 45.4 ± 11.2 years, body mass index 24.1 ± 4.28 kg/m2, and duration of diabetes 7.76 ± 5.77 years. The prevalence of subclinical hypothyroidism and overt hypothyroidism was 23/100 (23%) and 3/100 (3%), respectively. Thyroid autoantibody was positive in 13 (13.1%) patients. All patients were iodine sufficient. A trend toward increased neuropathy (r = 0.45) and nephropathy (r = −0.29) was associated with rising TSH. Conclusion: Almost one in four people living with diabetes are suffering from TD. Thus, routine screening should be implemented. Salt iodination program is a huge success in this part of the country.

The world is currently facing a diabesity and hypertension pandemic. Increased per capita calorie intake, especially refined sugars, are driving this pandemic, especially in the developing world. Replacement of saturated fats with unsaturated fats or carbohydrates especially refined sugars reduces cardiovascular (CV) risk. Very low intake of saturated fats (

To evaluate ovarian function after total abdominal hysterectomy in premenopausal women.In the present cross-sectional study, we enrolled 52 healthy female subjects having normal menstrual cycle as controls and 37 female patients (age45 years) who had undergone total abdominal hysterectomy (TAH) with preservation of at least one ovary for the evaluation of ovarian function. Serum antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay in both groups. Transvaginal Doppler ultrasonography was done to measure ovarian stromal blood flow indices (resistive index [RI] and pulsatility index [PI]). The means obtained from different sample groups were compared using the nonparametric Mann-Whitney U test, and correlations between two variables were evaluated using the Spearman nonparametric correlation test. A value of P.05 was considered statistically significant.Mean postoperative duration of patients who had undergone hysterectomy was 2.5 years. Mean serum AMH level was 7.68 ± 6.70 ng/mL in the cases, significantly lower than the level in controls (10.98 ± 7.83 ng/mL) (P = .016). Serum FSH level in controls was 12.01 ± 6.27 μIU/mL, which was significantly higher in the cases (20.27 ± 12.91 μIU/mL) (P = .001). An inverse correlation between serum AMH and FSH was observed (P = .0006; r = -0.4583). However, the ovary RI and PI values in both groups were similar.TAH affects ovarian function, despite normal ovarian blood supply.AMH = antimüllerian hormone FSH = follicle-stimulating hormone RI = resistive index PI = pulsatility index TAH = total abdominal hysterectomy.

Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) and dysglycemia are public health challenges. There is urgent need for anthropometric surrogates for NAFLD screening. This study evaluated role of neck circumference (NC) and neck-height ratio (NHtR) as predictors of liver stiffness measure (LSM) in individuals with prediabetes (IPD). Methods: In a cross-sectional study, 188 IPD from 1130 screened individuals underwent anthropometry, ultrasonography, Fibroscan® for LSM, dyslipidemia, insulin resistance (IR), and fetuin-A assessment. Results: Hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), metabolic syndrome (MetS), NAFLD, and significant liver stiffness (SLS) (LSM >8.5kPa) were observed in 53.7%, 31.4%, 71.3%, 73.9%, 24.5%, and 11.2% prediabetes individuals, respectively. Prediabetes with NAFLD had significantly higher body mass index (BMI), NC, NHtR, glycated hemoglobin, triglycerides, fatty liver index (FLI), and LSM. Prediabetes in highest NHtR quartile had significantly higher BMI, hypertension, MetS, fasting glucose, glycated hemoglobin, homeostatic model assessment-IR, NAFLD, LSM, SLS, and lower HDL-C. Stepwise forward linear regression revealed that NHtR, FLI, and LDL-C were best predictors of LSM, at baseline (Model-1), after adjusting for age and sex (Model-2), and adjusting model-2 plus systolic and diastolic blood pressure (Model-3). NHtR and NC (in females) and NHtR and BMI (in males) had largest area under the curves for predicting LSM, NAFLD, and MetS. NHtR ≥21.54 cm/m (sensitivity: 90%; specificity: 52.5%; females) and ≥21.62 cm/m (sensitivity: 80%; specificity: 49.4%; males) was best predictor of SLS. Interpretation and Conclusion: NHtR is a reliable tool for community screening of NAFLD and liver stiffness in prediabetes.

Background and Aims: Although Vitamin D deficiency has been linked to autoimmune thyroid disorders (AITD), the impact of Vitamin D supplementation on thyroid autoimmunity is not known. This study aimed to evaluate the impact of Vitamin D supplementation on thyroid autoimmunity (thyroid peroxidase antibody [TPO-Ab] titers) in patients with newly diagnosed AITD in a randomized controlled trial. Materials and Methods: One hundred two patients with newly diagnosed AITD (TPO-Ab > 34 kIU/L and/or sonographic evidence of thyroiditis) patients were randomized into Group-1 (intervention group) and Group-2 (control group). Group-1 received cholecalciferol 60,000 IU weekly and calcium 500 mg/day for 8 weeks; Group-2 received calcium 500 mg/day for 8 weeks. Responders were defined as ≥25% fall in TPO-Ab titers. Individuals with at least 3-month follow-up were analyzed. Trial is registered at ctri.nic.in (CTRI/2015/04/005713). Results: Data from 100 AITD patients (68 with thyroid stimulating hormone [TSH] ≤10 mIU/L, 32 with TSH > 10 mIU/L), 93% having Vitamin D insufficiency, were analyzed. TPO-Ab titers were highest among patients in the lowest 25-hydroxyvitamin D quartile (P = 0.084). At 3 months follow-up, there was significant fall in TPO-Ab in Group-1 (−46.73%) as compared to Group-2 (−16.6%) (P = 0.028). Sixty-eight percentage patients in Group-1 were responders compared to 44% in Group-2 (P = 0.015). Kaplan–Meier analysis revealed significantly higher response rate in Group-1 (P = 0.012). Significantly greater reduction in TPO-Ab titers was observed in AITD with TSH ≤ 10 mIU/L compared to TSH > 10 mIU/L. Cox regression revealed Group-1 followed by TPO-Ab and free tetraiodothyronine levels to be a good predictor of response to therapy (P = 0.042, 0.069, and 0.074, respectively). Conclusion: Vitamin D supplementation in AITD may have a beneficial effect on autoimmunity as evidence by significant reductions in TPO-Ab titers.

Objective Cardiovascular events are the most common cause of mortality in Cushing syndrome (CS). This study aimed to evaluate the impact of novel factors on atherosclerosis in endogenous CS. Methods A total of 22 female patients with CS and 33 normal female controls underwent evaluation of fibrinogen, high-sensitivity C-reactive protein (hsCRP), inflammatory cytokines (interleukin [IL]-6, IL-1β, soluble tumor necrosis factor receptor [sTNFR]-1, and sTNFR2), glu-tathione peroxidase (GPx; measure of oxidative stress), carotid intima media thickness (CIMT; a measure of atherosclerosis), and percent change in flow-mediated vasodilation (%FMV) of the brachial artery, a measure of endothelial dysfunction. Stepwise multiple linear regressions were done after adjusting for variables in models 1 through 3 to evaluate their role in predicting CIMT and %FMV. Model 1 consisted of age and body mass index (BMI). Model 2 consisted of model 1 plus blood pressure (BP), fasting blood glucose (FBG), and 2-hour postglucose blood glucose (2hPGBG). Model 3 consisted of model 2 plus triglycerides and low- and high-density lipoprotein. Results: Females with CS had significantly higher BMI, BP, FBG, 2hPGBG, total cholesterol, triglycerides, fibrinogen, IL-6, IL-1β, sTNFR1, and GPx. CIMT and %FMV were significantly higher and lower, respectively, in CS patients. Regression analyses revealed sTNFR1 to be a consistent predictor of CIMT after adjusting for model 1 (β = 0.656; P = .004), model 2 (β = 0.571; P = .047), and model 3 (β = 0.683; P = .026). GPx was a predictor of CIMT after adjusting for model 1 (β = 0.565; P = .033) and model 3 (β = 0.756; P = .038). Conclusion This study highlights increased CIMT and endothelial dysfunction in CS, associated with an altered inflammatory milieu. sTNFR1 and GPx may predict CIMT in females with CS. (Endocr Pract. 2015;21:286-295)

Background: Interpretation of thyroid function tests during pregnancy depends on gestational age, method, and population-specific reference intervals. Therefore, there is a worldwide trend to establish trimester-specific levels for different populations. The aim of this study was to establish a trimester-specific reference range for thyroid function parameters during pregnancy in Indian women.Materials and Methods: Thyroid function tests (TSH, FT4, TT4, TT3) of 80, 76, and 73 women at 1st, 2nd, and 3rd trimester, respectively, and 168 nonpregnant women were analyzed after exclusion of low UIC(&#60150 μg/L) and anti-TPO positivity(>35 IU/ml). Urinary iodine excretion (UIC) was assessed in all. The 2.5th and 97.5th percentile values were used to determine the reference ranges for thyrotropin (TSH), free thyroxine (FT4), total thyroxine (TT4), and total triiodothyronine (TT3) for each trimester of pregnancy. Results: The reference range for TSH for first trimester was 0.19–4.34 μIU/ml, for second trimester 0.46–4.57 μIU/ml, and for third trimester 0.61–4.62 μIU/ml. The reference range during three trimesters for FT4 (ng/dl) was 0.88–1.32, 0.89–1.60, and 0.87–1.54, for total T4 (μg/dl) was 5.9–12.9, 7.4–15.2, and 7.9–14.9. In nonpregnant women, FT4 was 0.83–1.34, total T4 was 5.3–11.8, and TSH was 0.79–4.29. The mean UIC in nonpregnant women was 176 ± 15.7 μg/L suggesting iodine-sufficiency in the cohort. Conclusion: The trimester-specific TSH range in pregnant women in this study is not significantly different from nonpregnant reference range in the final phase of transition to iodine sufficiency in India.

Background Type 1 diabetes is associated with several disease-related and other organ-specific autoimmune disorders. Data related to various auto-antibodies in Type 1 diabetes in India is limited. Materials and methods In this cross sectional study, 92 subjects with T1DM (33 males, 59 females) were evaluated for T1DM related antibodies (autoantibodies to glutamic acid decarboxylase (anti-GAD), autoantibodies to protein tyrosine phosphatise (anti-IA2), anti-islet cell antibody (ICA), insulin autoantibody (IAA), anti-Zinc Transporter(ZnT8) and other organ specific auto antibodies like anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TgAb), IgA anti-tissue transglutaminase (IgA anti-tTG), anti-21-hydroxylase, and anti-ovarian antibody (in females). Results Anti-GAD, IA-2, islet cell antibody, insulin autoantibodies (IAA), ZnT8 antibody were present in 79.3%, 32.6%, 61.9%, 63%, and 20.65% subjects, respectively. Only 2.2% patients with Type 1 diabetes were antibody negative. At least one antibody was found in 97.8% and at least two antibodies in 67.3%. The presence of anti-TPO, anti-thyroglobulin, IgA anti-tissue transglutaminase, anti 21-hydroxylase were found in 51%, 25%, 22.8%, and 2.1%, respectively. Anti-ovarian antibody was absent in all females of our study population. The duration of diabetes positively correlated with the number of T1DM specific antibody and also with GAD antibody positivity. Anti TPO positivity correlated with the age of onset of T1DM, but not with the duration of disease or presence of other T1DM specific autoantibody. Conclusions T1DM is associated with a high prevalence of autoantibodies and antibody negative T1DM is rare. The association with other organ specific antibody (especially thyroid and adrenal glands) and celiac disease is also substantial, which reinforces the importance of regular thyroid and celiac disease screening in T1DM subjects. The duration of diabetes positively correlated with number of T1DM specific antibodies.

Objective Fetuin-A is a novel hepatokine. The number of biologic roles attributed to fetuin-A has increased exponentially in the past decade. The objective of this review is to discuss the pathophysiology of fetuin-A action, its proinflammatory and antiinflammatory attributes in different biological systems throughout the body, and pharmacologic interventions that modulate fetuin-A levels. Methods PubMed, Medline, and Embase search for articles published to July 2014, using the terms “alpha-2-hs-glycoprotein” [MeSH Terms] OR “alpha-2-hs-glyco-protein” [All Fields] OR “fetuin a” [All Fields]. Results Fetuin-A is the endogenous ligand for Toll-like receptor-4 activation, for lipid-induced insulin resistance. Fetuin-A has inverse interaction with adiponectin. Increased fetuin-A is a risk factor for diabetes and fatty liver disease in normoglycemia and prediabetes. Fetuin-A is a negative acute-phase reactant in sepsis and endotoxemia, promotes wound healing, and is neuroprotec-tive in Alzheimer’s disease. Decreased fetuin-A predicts increased disease activity in obstructive lung disease, Crohn’s disease, and ulcerative colitis. Both elevated and reduced fetuin-A may be linked with increased cardiovascular events. Conclusion Fetuin-A is a pleotropic molecule with diverse (sometimes even contradictory) effects in different systems, brought about by interaction with a variety of receptors, including the insulin, transforming growth factor-β, and a plethora of Toll-like receptors. As a proinflammatory molecule, fetuin-A contributes to insulin resistance and is an important link between liver, adipose tissue, and muscles. Fetuin-A is neuroprotective and plays an important antiinflammatory role in sepsis and autoimmune disorders. Pharmacologic options are limited in modulating serum fetuin-A, but salsalates, curcumin, and vitamin D are promising agents of the future. (Endocr Pract. 2014;20:1345-1351)

Background The relationship between albumin : creatinine ratio (ACR), insulin resistance (IR), cytokines, dyslipidemia, and 25-hydroxy vitamin D (25-OHD) in individuals with prediabetes (IPD) was investigated to evaluate their role in predicting future risk of progression to diabetes. Methods The aforementioned parameters were evaluated in 147 IPD with persistent impaired fasting glucose and/or impaired glucose tolerance over two oral glucose tolerance tests, who were then followed up at 3-monthly intervals for progression to diabetes or reversal to normoglycemia. Results Data were analyzed for 137 IPD with at least 1-year follow-up. Forty-three IPD reversed to normoglycemia (Group I), 69 continued with prediabetes (Group II), and 25 progressed to diabetes (Group III) over a mean follow-up period of 28.36 ± 8.19 months. Baseline fasting blood glucose levels (BGLs), 2-h post-glucose BGLs, and ACR were lowest in Group I and highest in Group III. Of the 137 IPD, 54.75% (n = 75) had microalbuminuria. The IPD in the lowest ACR quartile had the highest reversal to normoglycemia. Cox regression revealed that baseline IL-6 was predictive of progression to diabetes (P = 0.03) and ACR was an independent predictor of reversal to normoglycemia (P = 0.007). Kaplan–Meier analysis showed higher reversal to normoglycemia in IPD without microalbuminuria (P

Aim To evaluate the role of fetuin-A levels in predicting glycaemic outcomes (progression to diabetes or reversion to normoglycaemia) in people with prediabetes. Methods A total of 2119 people were screened, of whom 144 people with prediabetes, 50 people with normoglycaemia and 66 people with newly diagnosed diabetes underwent estimation of fasting insulin, fetuin-A, interleukin-6, interleukin-1β, tumour necrosis factor-α, lipid and 25-hydroxyvitamin-D levels and assessment of non-alcoholic fatty liver disease using ultrasonography and the fatty liver index. People with prediabetes were followed and analysed according to glycaemic outcome and quartile of fetuin-A level. Results Fetuin-A, interleukin-1β, interleukin-6, tumour necrosis factor-α and triglyceride levels and presence of non-alcoholic fatty liver disease increased across the glycaemic spectrum and were highest in people with diabetes. A total of 32 people with prediabetes reverted to normoglycaemia, 23 progressed to diabetes and 65 remained with prediabetes over a mean ± sd follow-up of 32.12 ± 8.4 months. People progressing to diabetes had higher baseline glycaemia rates, fetuin-A levels, interleukin-1β levels, fatty liver index scores and prevalence of non-alcoholic fatty liver disease and lower 25-hydroxyvitamin-D levels. People with prediabetes in the highest fetuin-A quartile had the highest risk of progression to diabetes (relative risk 2.68, 95% CI 0.95–7.55; P = 0.06) and the lowest rate of reversion to normoglycaemia (relative risk 0.27, 95% CI 0.08–0.85; P = 0.03). Fetuin-A levels correlated with interleukin-1β levels (r = 0.420; P

Vitamin-D supplementation in vitamin-D insufficient/deficient prediabetes individuals is associated with significantly lower progression to diabetes (6/55 vs. 13/49; p=0.04) and higher reversal to normoglycemia (23/55 vs. 10/49; p=0.02), associated with decreased insulin resistance and systemic inflammation (TNFα and IL6). Baseline vitamin-D and 2h blood glucose independently predicted progression to diabetes.

Prediabetes (IPD; n =122) and normoglycemic individuals ( n =100) underwent assessment of polymorphisms of TNFα (−238, −308) and IL6 (−174). After 27.25±5.64 months, 16 IPD had reverted to normoglycemia and 18 progressed to diabetes. TNFα −238AA/GA genotypes were significantly more common in IPD, had higher TNFα, higher progression to diabetes and lower reversal.