Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

Early liraglutide treatment is better in glucose control, β-cell function improvement and mass preservation in db/db mice

Glucagon-like peptide-1 (GLP-1) has been proved to have effects of anti-hyperglycemia and β-cell preservation. However, it is still unclear whether there are differences between early and late GLP-1 intervention in type 2 diabetes mellitus (T2DM). We divided the mice into 5 groups: early treated group (n = 7, 8-week old, fasting glucose > 10 mmol/l), late treated group (n = 7, 10-week old, fasting glucose > 20 mmol/l), early control group (n = 7), late control group (n = 7) and wild type group (n = 7). Treated group was injected with liraglutide (a GLP-1 analog) 300 μg/kg bid for 4 weeks, while control group was given saline at the same time. The results showed that compared with control group, food intake and body weight gain were reduced in both early and late treated group (p < 0.05), and there was no significance between the two treated groups. Early liraglutide intervention showed better improvements in glucose control, acute insulin response to glucose (AIRg) and disposition index (before vs. after treatment, AIRg 1.01 ± 0.53 vs. 2.98 ± 0.63, disposition index 10.81 ± 0.89 vs. 27.4 ± 2.15) than late intervention (AIRg 0.99 ± 0.02 vs. 1.41 ± 0.32, disposition index 3.47 ± 0.38 vs. 6.43 ± 1.62, p = 0.001). The histopathology of the pancreas showed the estimated β-cell mass (BCM) was increased more in early treated group than that in late one (0.03 vs. 0.01 g). Expressions of the proliferation related genes PDX-1, MafA and GLP-1 receptor (GLP-1R) in early treated group were 1.81, 2.57 and 1.59 times as much as that in late treated group. In conclusion, early liraglutide intervention was better in glucose control, β-cell function improvement and β-cell mass preservation.     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)     

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM).Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m² vs. 21.9 ± 2.0 kg/m² vs. 21.4 ± 1.9 kg/m²; P>.05) were prospectively recruited.Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 μg/dL vs. 297 ± 100 μg/dL; P>.05).Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.     

Higher Growth Hormone Levels are Associated with Erectile Dysfunction in Male Patients With Acromegaly

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly.Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls.Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 μg/L &lsqb;interquartile range of 9.5 to 34.5 μg/L] versus 5.9 μg/L &lsqb;interquartile range of 3.4 to 13.9 μg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 μg/L for random GH and 5.3 μg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 μmol/L versus 19.19 ± 5.02 μmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 μmol/L versus 12.09 ± 3.44 μmol/L; P = .027).Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required.Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic     

Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)     

Hypoglycemic effect of aspalathin,a rooibos tea component from Aspalathus linearis,in type 2 diabetic model db/db mice

Effects of aspalathin, a green rooibos tea component, on glucose metabolism were studied in vitro and in vivo. We first examined the effect of aspalathin on glucose uptake by cultured L6 myotubes and on insulin secretion from cultured RIN-5F pancreatic β-cells in vitro, and then investigated the effect of dietary aspalathin on fasting blood glucose level and conducted an intraperitoneal glucose tolerance test (IPGTT) using type 2 diabetes model mice in vivo. Aspalathin dose-dependently and significantly increased glucose uptake by L6 myotubes at concentrations 1–100 μM. It also significantly increased insulin secretion from cultured RIN-5F cells at 100 μM. Dietary aspalathin (0.1–0.2%) suppressed the increase in fasting blood glucose levels of db/db mice for 5 weeks. In IPGTT, aspalathin improved impaired glucose tolerance at 30, 60, 90, and 120 min in db/db mice. These results suggest that aspalathin has beneficial effects on glucose homeostasis in type 2 diabetes through stimulating glucose uptake in muscle tissues and insulin secretion from pancreatic β-cells.     

Serum zinc is associated with plasma leptin and Cu–Zn SOD in elite male basketball athletes

This paper investigates the relationship between plasma trace element and plasma leptin, as well as percent fat mass, in 16 male basketball athletes. Blood samples were obtained before intensive training and 24 h after intensive training to measure plasma zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), iron (Fe), and leptin levels. High-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), total and cholesterol (TC) levels were determined using commercially available kits for humans. Subjects presented similar values in terms of age (21.1 ± 2.2 years old), body mass index (23.9 ± 2.00 kg/m²), percent body fat (14.40 ± 1.52%), plasma hemoglobin (150.1 ± 9.4 g/L), plasma Zn (17.47 ± 1.28 μmol/l), plasma Cu (13.42 ± 1.40 μmol/L), plasma Ca (2.41 ± 0.14 mmol/L), and plasma Mg (0.96 ± 0.02 mmol/L). The correlation analysis between degree of plasma leptin and plasma element contents was performed using the SPSS 16.0 software. Plasma Zn correlated positively with plasma leptin (r = 0.746, P < 0.01), Cu–Zn SOD (r = 0.827, P < 0.01), and negatively with percent fat mass (r = –0.598, P < 0.05) under no-training conditions. Meanwhile, plasma Cu, Ca, Mg, and Fe did not correlate with plasma leptin or percent fat mass (P > 0.05). In conclusion, plasma Zn may be involved in the regulation of plasma leptin and may serve as a lipid-mobilizing factor in Chinese men's basketball athletes.     

Serum sialic acid changes in non-insulin-dependant diabetes mellitus (NIDDM) patients following bitter melon (Momordica charantia) and rosiglitazone (Avandia) treatment

Diabetes mellitus is associated with an increase in sialic acid concentration along with other complications. Sialic acid changes in NIDDM patients were investigated following bitter melon (55 ml/24 h) and rosiglitazone (4 mg/24 h) treatment. A total of 25 patients of both sexes were used in each experimental group. Patients following bitter melon treatment showed no significant difference of serum sialic acid (57.95±4.90 vs. 57.6±5.56 mg/dl, p=0.17) and serum glucose concentration (93.7±9.63 vs. 88.35±6.31 mg/dl, p=0.78) as compared to control subjects. However, the concentration of total cholesterol was significantly high in these patients as compared to control subjects (192±14.23 vs. 170.6±15.1 mg/dl, p<0.03) but within normal range (160–200 mg/dl), suggesting the significant hypoglycemic and lipid-lowering properties of bitter melon. The patients following rosiglitazone treatment showed a significant increase of serum sialic acid concentration (60.2±5.80 vs. 57.6±5.56 mg/dl, p=0.01) along with glucose (112±6.2 vs. 88.35±6.31 mg/dl, p<0.04) and total cholesterol concentration (216.45±20.2 vs. 170.6±15.1 mg/dl, p<0.01) as compared to control subjects. In addition six of the patients had retinopathy, two of whom were suffering also from myocardial infarction and they still had a higher serum sialic acid (61.05±1.20 mg/dl), glucose (187±2.11 mg/dl), total cholesterol (239.10±5.04 mg/dl) and triglyceride (183±4.14 mg/dl) concentration, indicating a poor response of these patients to rosiglitazone. Comparison of serum sialic acid concentration of patients, following bitter melon and rosiglitazone treatment revealed no significant difference but the study showed that bitter melon could be more effective in the management of diabetes and its related complications as compared to rosiglitazone.     

Clinical Markers Implying the Need for Treatment in Women with Gestational Diabetes Mellitus

ObjectiveTo assess the association of the point-of-care hemoglobin A_1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM).MethodsPOC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication.ResultsMean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P < .001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P < .001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m2 [P < .001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P < .001) and between POC A1C and BMI (Spearman rho 0.366, P < .001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho –0.010, P = .915).ConclusionsHigher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications. (Endocr Pract. 2012;18:62-65)     

Clinical Profile of Nonalcoholic Fatty Liver Disease Among Young Patients With Type 1 Diabetes Mellitus Seen at a Diabetes Speciality Center in India

ObjectiveTo estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India.MethodsElectronic medical records of T1DM patients (age at first diagnosis of T1DM ≤ 25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was > 500 mg/day, and neuropathy was diagnosed if a patient’s vibration perception threshold on biothesiometry was ≥ 20 V.ResultsA total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m², P < .001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P < .05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P < .001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P < .05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P < .05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P < .001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose.ConclusionsThis study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy. (Endocr Pract. 2014;20:1249-1257)     

Zinc and glycemic control: A meta-analysis of randomised placebo controlled supplementation trials in humans

BackgroundImpaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus.MethodsA systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011.ResultsFourteen reports (n = 3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (?0.19 ± 0.08 mmol/L, P = 0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (?0.64 ± 0.36%, P = 0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03 ± 0.81 μmol/L, P = 0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (?0.49 ± 0.11 mmol/L, P = 0.001) compared to the effect that was observed in healthy participants.ConclusionThe significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease.     

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9 ± 1.2 years, BMI: 34.2 ± 1.1 kg/m²) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60 min/day for 5 days/week at ∼85% HR_max). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40 mU/m²/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75 g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P < 0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P < 0.001) and decreased HOMA-IR by 15% (P < 0.05). Training decreased plasma DPP-4 by 10% (421.8 ± 30.1 vs. 378.3 ± 32.5 ng/ml; P < 0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r = −0.59; P < 0.04), HOMA-IR (r = 0.59; P < 0.04) and fat oxidation (r = −0.54; P < 0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r = −0.64; P < 0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome.     

Embryo production and progesterone profiles in ewes superovulated with different hormonal treatments

The superovulatory response and embryo yield following hormonal treatments of Merino ewes during late spring and their estrous cycle were evaluated. Ewes (n=17) were treated with progestagen-impregnated sponges and assigned to Group I (800 IU PMSG plus 11.5 mg FSH-p); Group II (1200 IU PMSG); Group III (1600 IU PMSG). Ewes were naturally mated and followed by laparotomy 6 days later. After laparotomy, ewes were injected with a prostaglandin analogue (PGF) and serum samples were obtained prior to surgery and then for 25 days to measure progesterone (P4) by radioimmunoassay. There were no differences among groups neither for estrous incidence (Group I: 83.3%; Group II: 83.3%; Group III: 100%), nor for the time interval to estrous onset (Group I: 26.4±2.4 h; Group II: 28.8±2.9 h; Group III: 24.0±3.8 h). Group I had more corpora lutea than Group II (14.2±1.2 and 6.2±0.8; P<0.05), and Group III was intermediate (11.0±3.0). There was a low incidence of persistent follicles in all treatments (Group I: 0.5±0.5; Group II: 0.6±0.4; Group III: 1.8±1.2). Number of collected ova were 9.0±2.6, 3.8±0.6 and 6.5±0.9 for Groups I, II and III, respectively. Significant differences in number of ova were detected between Groups I and II. Unfertilized ova did not differ among groups (Group I: 3.5±1.0; Group II: 2.8±0.8; Group III: 5.2±1.4; P>0.05). Embryos and high viability embryos were higher (P<0.05) in Group I (5.2±1.9 and 4.8±2.0) than in Group II (1.0±0.5 and 1.0±0.5) or Group III (1.2±0.6 and 1.0±0.5). Total plasma progesterone (P4) and P4 per corpus luteum before PGF administration did not vary (P>0.05) among groups (Group I: 71.0±14.7 and 4.9±0.7 nmol/l; Group II: 50.6±13.3 and 7.9±1.6 nmol/l; Group III: 90.4±42.6 and 6.8±1.8 nmol/l). There was a significant and positive correlation between P4 before PGF administration and number of corpora lutea (r=0.76). No significant differences were detected among groups for: interval PGF to P4 <3.18 nmol/l (Group I: 2.7±0.3 days; Group II: 1.8±0.6 days; Group III: 2.2±0.5 days), cycle length (Group I: 18.3±1.4 days; Group II: 17.9±0.5 days; Group III: 16.8±0.9 days), duration of P4 levels <3.18 nmol/l (Group I: 11.3±1.9 days; Group II: 7.1±1.0 days; Group III: 7.2±2.4 days), duration of P4 levels ≥3.18 nmol/l (Group I: 7.0±1.3 days; Group II: 10.8±0.8 days; Group III: 9.5±1.7 days) and peak of P4 (Group I: 7.4±0.4 nmol/l; Group II: 10.8±1.6 nmol/l; Group III: 9.2±1.9 nmol/l). It was concluded that PMSG–FSH-p treatment was more efficient than PMSG alone for superovulation and embryo production in ewes while P4 profiles were similar among groups.     

Peroxidación lipídica en la membrana de los linfocitos y oxidación proteica en el suero de personas ancianas, ¿marcadores potenciales de fragilidad y dependencia? Resultados preliminares

ObjectiveTo study the relationships between lipid peroxidation of the lymphocyte membrane, protein oxidation and different markers of frailty and dependence.MethodsThe sample consisted of 15 elderly patients in an intermediate and long-term care center, who had not suffered any acute process recently. The geriatric assessment included, functional capacity (Barthel and Lawton indexes), comorbidity (Charlson index), and cognitive function (Mini Mental State Examination of Folstein). The frailty was estimated by the Hospital Admission Risk Profile (high risk of frailty 4-5 points, intermediate/low 0-3 points) and Frailty Scale of Rockwood (mild frailty < 6, intermediate frailty/severe ≥ 6). Lipid peroxidation was studied by determination of conjugated dienes and trienes. Analysis of protein oxidation was performed by determining malondialdehyde bound to plasma proteins, corrected by total protein quantification.ResultsElderly patients at high risk of frailty according to Hospital Admission Risk Profile presented mean values of conjugated dienes of 7.94 ± 1.32%, trienes of 1.75 ± 0.51%, and malondialdehyde bound to plasma proteins of 141.9 ± 27.3 nmol/g. In the group of intermediate/low risk, these values were 4.96 ± 2.77% (P = .035), 1.37 ± 0.78% (P = .337) and 96.4 ± 31.5 nmol/g (P = .022), respectively. In those with intermediate/severe frailty according to the Frailty Scale of Rockwood, these values were 7.06 ± 2.18%; 1.73 ± 0.50% and 119.6 ± 37.9 nmol/g, respectively, and in those with mild frailty 2.56 ± 1.48% (P = 014); 0.61 ± 0.58% (P = 020) and 173.2 ± 51.9 nmol/g (P = .144), respectively. There was good correlation between the Hospital Admission Risk Profile score and malondialdehyde bound to plasma proteins (r = 0.70; P = 01) and between the Frailty Scale of Rockwood score and conjugated dienes (r = 0.65; P = 01).ConclusionsElderly patients with a higher degree of frailty appear to have greater levels of lipid peroxidation, which could be considered a marker of frailty.     

Nutrient concentrations in tidal creeks as indicators of the water quality role of mangrove wetlands in Southwest Florida

Coastal mangroves have the potential to improve the water quality of urban and rural runoff before it is discharged into adjacent coastal bays and oceans; but they also can be impaired by excessive pollutants from upstream. Nutrients (phosphorus and nitrogen), salinity, and other water quality parameters were measured in five mangrove tidal creeks in different hydrogeomorphic and urbanization settings during high and low tides over a calendar year of wet (June and August 2015) and dry (February and April 2016) seasons in the Greater Naples Bay area in Southwest Florida, USA. Nutrient concentrations (ave. ± std error) in the tidal creeks were 0.055 ± 0.008 mg-P/L for total phosphorus (TP) and 0.610 ± 0.020 mg-N/L for total nitrogen (TN), with an average N:P ratio of 11.4:1. Average wet season TP (0.075 ± 0.010 mg-P/L) was significantly higher than the dry season TP (0.033 ± 0.003 mg-P/L; p < 0.01, f = 15.17, f_crit = 3.89) and the average wet season TN (0.75 ± 0.03 mg-N/L) was significantly higher than dry season TN (0.52 ± 0.02 mg/L; p < 0.01, f = 64.14, f_crit = 3.89), suggesting that urban stormwater runoff is directly or indirectly affecting the nutrient conditions in these mangroves. Significant differences in nutrient concentrations between low tide and high tide were not found for either TP (p = 0.43, f = .63, f_crit = 3.88) or TN (p = 0.20, f = 1.66, f_crit = 3.89). These differences were confirmed by a PCA and cluster analyses, which found differences to be seasonal. We could not conclude from these results whether these five mangrove wetlands were sources nor sinks of nutrients based simply on the measurement of nutrient concentrations. But we illustrated that nutrient concentrations were indicators of the mangroves’ hydrogeomorphic settings, their tidal fluxes from Naples Bay, and the Bay's upstream watersheds, and less by direct urban runoff.     

The effects of mitochondrial complex I blockade on ATP and permeability in rat pulmonary microvascular endothelial cells in culture (PMVEC) are overcome by coenzyme Q1 (CoQ1)

In isolated rat lung perfused with a physiological saline solution (5.5 mM glucose), complex I inhibitors decrease lung tissue ATP and increase endothelial permeability (K_f), effects that are overcome using an amphipathic quinone (CoQ₁) [Free Radic. Biol. Med. 65:1455–1463; 2013]. To address the microvascular endothelial contribution to these intact lung responses, rat pulmonary microvascular endothelial cells in culture (PMVEC) were treated with the complex I inhibitor rotenone and ATP levels and cell monolayer permeability (PS) were measured. There were no detectable effects on ATP or permeability in experimental medium that, like the lung perfusate, contained 5.5 mM glucose. To unmask a potential mitochondrial contribution, the glucose concentration was lowered to 0.2 mM. Under these conditions, rotenone decreased ATP from 18.4±1.6 (mean±SEM) to 4.6±0.8 nmol/mg protein, depolarized the mitochondrial membrane potential (Δψ_m) from −129.0±3.7 (mean±SEM) to −92.8±5.5 mV, and decreased O₂ consumption from 2.0±0.1 (mean±SEM) to 0.3±0.1 nmol/min/mg protein. Rotenone also increased PMVEC monolayer permeability (reported as PS in nl/min) to FITC–dextran (~40 kDa) continually over a 6 h time course. When CoQ₁ was present with rotenone, normal ATP (17.4±1.4 nmol/mg protein), O₂ consumption (1.5±0.1 nmol/min/mg protein), Δψ_m (−125.2±3.3 mV), and permeability (PS) were maintained. Protective effects of CoQ₁ on rotenone-induced changes in ATP, O₂ consumption rate, Δψ_m, and permeability were blocked by dicumarol or antimycin A, inhibitors of the quinone-mediated cytosol–mitochondria electron shuttle [Free Radic. Biol. Med. 65:1455–1463; 2013]. Key rotenone effects without and with CoQ₁ were qualitatively reproduced using the alternative complex I inhibitor, piericidin A. We conclude that, as in the intact lung, PMVEC ATP supply is linked to the permeability response to complex I inhibitors. In contrast to the intact lung, the association in PMVEC was revealed only after decreasing the glucose concentration in the experimental medium from 5.5 to 0.2 mM.     

Insulin-releasing and cytotoxic properties of the frog skin peptide,tigerinin-1R: a structure–activity study

The frog skin host-defense peptide tigerinin-1R (RVCSAIPLPICH.NH₂) is insulinotropic both in vitro and in vivo. This study investigates the effects on insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P < 0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01 nM compared with 0.1 nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3 μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P < 0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC₅₀ = 265 ± 16 μM) and inhibited growth of Escherichia coli (MIC = 500 μM) and Staphylococcus aureus (MIC = 250 μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75 nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P < 0.05) enhanced insulin release and improved glucose tolerance over a 60 min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus.     

Biochemical changes in the follicular fluid of the dominant follicle of high producing dairy cows exposed to heat stress early post-partum

High yielding dairy cows experience a negative energy balance (NEB) early post-partum and it was hypothesized that this may be aggravated under summer heat stress (HS) conditions. In this study, which was performed in Egypt, 20 Holstein cows were followed during summer (n = 10) and winter (n = 10) seasons. All cows were multiparous and kept at the same herd. Blood was sampled from each cow starting 1 week before the expected calving date and then at 1-week intervals until week 6 post-partum. From week 2 to 6 post-partum follicular fluid was collected through transvaginal follicular fluid aspiration at 6 days intervals. Ambient air temperature (AT) and relative humidity (RH) were recorded and temperature–humidity index (THI) was calculated as well. Respiration rate (RR), rectal temperature (RT), and body condition score (BCS) were recorded for each cow at the time of blood sampling. Concentrations of glucose, insulin like growth factor-1 (IGF-1), non-esterified fatty acids (NEFA), urea and total cholesterol (TC) were measured in each blood and follicular fluid sample. All the cows showed a significantly higher RR and RT in summer (95.5 ± 1.1 and 39.88 ± 0.06, respectively) than in winter (43.89 ± 0.61 and 38.94 ± 0.07, respectively) (P < 0.001). Body condition score loss during the early post-partum period was higher in summer than in winter (1.1 ± 0.07 vs. 0.85 ± 0.06 point, respectively) (P < 0.001). The average dominant follicle diameter was significantly lower in summer than in winter during the period of negative energy balance (11.6 ± 0.7 mm vs. 15.3 ± 1.2 mm, respectively) (P < 0.01). Under summer heat stress, the concentrations of glucose (2.98 ± 0.07 and 2.19 ± 0.04 mmol/L), IGF-1 (106.7 ± 2.9 and 99.0 ± 3.4 ng/ml) and TC (137.3 ± 5.3 and 62.2 ± 5.1 mg/dl) in blood and FF, respectively, were significantly lower than winter concentrations by (0.17 ± 0.03 mmol/L, P < 0.001 and 0.26 ± 0.06 mmol/L, P < 0.001), (12.3 ± 3.6 ng/ml, P < 0.001 and 9.0 ± 2.7 ng/ml, P < 0.001) and (20.7 ± 1.8 mg/dl, P < 0.001 and 7.3 ± 1.1 mg/dl, P < 0.01), respectively. However, the concentrations of NEFA (0.68 ± 0.14 and 0.22 ± 0.02 mmol/L) and urea (9.27 ± 0.34 and 9.96 ± 0.25 mmol/L) in blood and FF, respectively, were significantly higher in summer compared to winter (0.50 ± 0.08 mmol/L, P < 0.001 and 0.20 ± 0.02 mmol/L, P < 0.001) and (8.77 ± 0.23 mmol/L, P < 0.05 and 8.96 ± 0.29 mmol/L, P < 0.001), respectively, throughout the experimental period. The results of the present study indicate that heat stress early post-partum aggravates NEB in high yielding dairy cows, reduces BCS, dominant follicle diameter and alters the biochemical concentrations in the follicular fluid of the dominant follicle which may result in inferior oocyte and granulosa cell quality and hence poorer fertility.     

Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes: Correlation with Carotid Intima Media Thickness

ObjectiveWe investigated the correlation between the severity of diabetic retinopathy (DR) and carotid intima media thickness (IMT) as a marker of atherosclerosis in patients with type 2 diabetes.MethodsThe study group consisted of 140 normo-tensive Egyptian patients (68 males and 72 females) with type 2 diabetes and DR. Carotid IMT was evaluated using high-resolution B-mode ultrasonography. DR was assessed and graded using colored fundus photography and fundus fluorescein angiography, as either nonproliferative DR (NPDR) or proliferative DR (PDR).ResultsCarotid IMT was greater in patients with PDR compared to those with NPDR (1.094 ± 0.142 mm vs. 0.842 ± 0.134 mm; P < .001). Carotid IMT showed positive correlation with diabetes duration (P < .01), systolic blood pressure (P < .001), diastolic blood pressure (P < .01), fasting blood glucose (P < .01), postprandial blood glucose (PPBG) (P < .001), glycated hemoglobin (P < .01), total cholesterol (P < .01), triglycerides (TGs) (P < .001), and DR (P < .0001). No significant difference was found between males and females in any of the studied parameters. Multiple regression analysis revealed that the determinants of carotid IMT in the studied group were age (P < .01), PPBG (P < .01), TGs (P < .001), and DR (P < .0001).ConclusionOur study proves that both NPDR and PDR are strong determinants of carotid IMT and atherosclerosis in patients with type 2 diabetes. (Endocr Pract. 2015;21:226-230)