Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study

Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.Design Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension.Setting Spanish university department.Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.Main outcome measures Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.     

Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes

The prevalence of obesity has grown to an alarming level of at least 300 million people worldwide. Additionally, a diabetes epidemic is underway, with an estimate of 217 million people with diabetes worldwide. There are many links between excessive body weight and type 2 diabetes, and one common and fundamental cause of both epidemics is an unhealthy diet. Research to identify and promote diets that protect individuals from obesity and type 2 diabetes is urgently needed. The Mediterranean diet, a concept developed in the 1950s, refers to dietary habits of individuals from the Mediterranean basin. The Mediterranean diet is an eating pattern that successfully combines pleasant taste and positive health effects. The Mediterranean diet does not stand for a homogenous and exclusive model among the Mediterranean basin population but rather represents a set of healthy dietary habits, including high consumption of vegetables and fresh fruits and the use of olive oil as the main source of fat. Evidence from epidemiological studies supports a protective effect of this dietary pattern on weight gain and the development of type 2 diabetes. Several mechanistic explanations link characteristic components of the Mediterranean diet with obesity and type 2 diabetes. This review will discuss potential mechanisms by which the Mediterranean diet protects individuals from both diseases.     

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the −4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D''= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.     

Does dietary magnesium modulate blood lipids?

In a randomized, single-blind, controlled study (400 patients aged 25-63 yr; 374 males, 26 females), 206 subjects were administered a magnesium-rich diet, and 194 subjects their usual diet, for 6 wk. Age, sex, body weight, hypertension, hyperlipidemia, smoking, obesity, diuretic therapy, and diabetes were comparable between the two groups, as were laboratory data at entry to the study. Intervention-group A received a significantly higher amount of dietary magnesium and potassium compared to group B, which received its usual diet. After 6 wk, there was a significant fall in total serum cholesterol (228.5 +/- 46.2 mg/dL), LDL cholesterol 146.5 +/- 75.5 mg/dL), and triglyceride (143.8 +/- 40.5 mg/dL) in group A compared to serum cholesterol (242.5 +/- 58.2 mg/dL), LDL cholesterol (157.0 +/- 78.4 mg/dL), and triglyceride (156.5 +/- 60.0 mg/dL) at entry to study, but no such changes in group-B subjects. HDL cholesterol showed a marginal mean decrease of 0.8 mg/dL in group B and a 2.5 mg/dL increase in group A. The changes in blood lipids were consistent with an increased intake of magnesium and with a rise in serum levels. Although a general blood-lipid-reducing effect of such a diet cannot be excluded, it is possible that dietary magnesium may have contributed to the reduction of total serum cholesterol, LDL cholesterol, and triglyceride, and the marginal rise in HDL cholesterol. More studies with longer follow-up periods are needed to confirm this observation.     

Metabolic Syndrome in Primary Gout

Background and Objectives. Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country. Patients and Method. All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels. Results. One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p < 0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444 ± 110 mg/24-hour/1,73 m² versus 546 ± 221 mg/day/1,73 m²; p = 0.009). Conclusions. The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.     

Fenofibrate Increases Serum Creatinine in a Patient with Familial Nephropathy Associated to Hyperuricemia

Background: Kidney function progressively deteriorates in patients with familial juvenile hyperuricemiac nephropathy (FJHN, OMIN 162000) and chronic renal disease is commonly associated to dyslipidemia. We report for the first time abrupt renal insufficiency in a patient with FJHN and hypertrygliceridemia following fenofibrate administration.Case report: A 53-year-old man was diagnosed clinically with FJHN at age 24 years which was subsequently confirmed by genotypic analysis of the UMOD gene at age 40 years. His mother and two brothers suffered the disease. At that time, renal size and function were normal, as was his blood pressure and serum lipids. At age 34 years, serum urate was 8.5 mg/dL and creatinine 1.7 mg/dL (GFR, 58 mL/min/1.73 m²). He was treated with allopurinol, losartan, and lovastatin. Serum TG levels ranged between 150 and 250 mg/dL. At age 52 years, serum urate was 4.1 mg/dL, creatinine 3.2 mg/dL, LDLc 99 mg/dL (atorvastatin 40 mg/d), and TG 275 mg/dL. Fenofibrate (160 mg/d) was added. One month later, serum creatinine increased to 4.2 mg/dL and TG decreased to 125 mg/dL. He did not complain of muscle pain, weakness, or changes in urinary frequency or color and rabdomyolysis was discarded. Fenofibrate was withheld and three months later serum creatinine decreased to baseline levels (3.2 mg/dL) and TG increased to 197 mg/dL.Conclusion: To our knowledge, this is the first patient with FJHN in whom fenofibrate administration was associated to a further impairment in renal function not attributable to rabdomyolysis.     

Effect of central and peripheral leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus)

Branched-chain amino acids, particularly leucine, are thought to activate nutrient sensing pathways in the hypothalamus that regulate food intake and energy homeostasis. In the light of recent controversial findings of leucine’s effect on energy homeostasis further clarification of the metabolic impact of dietary leucine supplementation is required. We examined the pharmacological and dietary effects of leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus), a well-established model for studies of alterations in leptin sensitivity and energy metabolism. We acutely administered leucine into the lateral ventricle (1.1 μg) of hamsters to characterize whether leucine exhibits anorexigenic properties in this species as has been described in other rodents. Next the catabolic effect of dietary administered leucine via supplemented rodent diet (15 % leucine), drinking water (17 g/L leucine) and oral gavages (10 mg/day); as well as the effect of subcutaneously (0.1 and 3 mg/day) and intraperitoneally (0.1, 3 and 6 mg/day) injected leucine which avoids the gastrointestinal-track was analyzed. Centrally administered leucine reduced 24 h food intake (by 32 %) and body weight. Both parameters were also reduced in hamsters with leucine supplemented diet, but this catabolic response was based on a pronounced taste aversion to the leucine-diet. In all other experiments, dietary leucine and peripheral injections of leucine had no effect on food intake, body weight and basal blood glucose levels. Our data suggest that in the Djungarian hamster dietary leucine fails to exhibit catabolic effects that would override the evolutionary conserved adaptations of the species which is critical for its survival.     

A 14-Item Mediterranean Diet Assessment Tool and Obesity Indexes among High-Risk Subjects: The PREDIMED Trial

OBJECTIVE: Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. DESIGN: Cross-sectional assessment of all participants in the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. SUBJECTS: 7,447 participants (55-80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or ≥3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. RESULTS: Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were -0.0066 (95% confidence interval, -0.0088 to -0.0049) for women and -0.0059 (-0.0079 to -0.0038) for men. The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥10 points versus ≤7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. CONCLUSIONS: A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk.     

Adipose DHA inversely associated with depression as measured by the Beck Depression Inventory

This study attempts to detect potential associations between depression and adipose docosahexaenoic acid (c22:6 n-3) (DHA), a valid indicator for long-term dietary intake of DHA, in a profoundly religious group that strictly adheres to the Orthodox Christian Church (OCC) rituals and lifestyle. A total of 24 strict fasters and 27 control subjects were included in the study. The two study groups did not differ with regard to depressive symptoms distribution. Adipose tissue DHA was inversely associated with depression, while adherence to the OCC diet was strongly correlated with adipose DHA levels compared to controls. In conclusion, increased long-term dietary DHA intake was associated with decreased depression occurrence, whereas adherence to the OCC dietary recommendations, which allows for frequent fish and seafood consumption, was associated with increased adipose and dietary DHA levels, known for their essential role on optimal neuronal function and protection against a number of chronic diseases.     

Selenium Supplementation Modulates Zinc Levels and Antioxidant Values in Blood and Tissues of Diabetic Rats Fed Zinc-Deficient Diet

Diabetes mellitus is associated to a reduction of antioxidant defenses that leads to oxidative stress and complications in diabetic individuals. The present study was undertaken to investigate the effect of selenium on blood biochemical parameters, antioxidant enzyme activities, and tissue zinc levels in alloxan-induced diabetic rats fed a zinc-deficient diet. The rats were divided into two groups; the first group was fed a zinc-sufficient diet, while the second group was fed a zinc-deficient diet. Half of each group was treated orally with 0.5 mg/kg sodium selenite. Tissue and blood samples were taken from all animals after 28 days of treatment. At the end of the experiment, the body weight gain and food intake of the zinc-deficient diabetic animals were lower than that of zinc-adequate diabetic animals. Inadequate dietary zinc intake increased glucose, lipids, triglycerides, urea, and liver lipid peroxidation levels. In contrast, serum protein, reduced glutathione, plasma zinc and tissue levels were decreased. A zinc-deficient diet led also to an increase in serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and liver glutathione-S-transferase and to a decrease in serum alkaline phosphatase activity and glutathione peroxidase. Selenium treatment ameliorated all the values approximately to their normal levels. In conclusion, selenium supplementation presumably acting as an antioxidant led to an improvement of insulin activity, significantly reducing the severity of zinc deficiency in diabetes.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Methadone-Induced Hypoglycemia

To determine if recent observations of hypoglycemia in patients receiving high-dose methadone extended to an animal model, we explored the effects of methadone and other mu-opioids on blood glucose levels in mice. Methadone lowered blood glucose in a dose-dependent manner with 20 mg/kg yielding a nadir in average glucose levels to 55 ± 6 mg/dL from a baseline of 172 ± 7 mg/dL, an effect that was antagonized by naloxone and mu selective antagonists β-funaltrexamine and naloxonazine. The effect was stereoselective and limited to only the l-isomer, while the d-isomer was ineffective. Despite the robust decrease in blood glucose produced by methadone, a series of other mu-opioids, including morphine, fentanyl, levorphanol, oxycodone or morphine-6β-glucuronide failed to lower blood glucose levels. Similar differences among mu-opioid agonists have been observed in other systems, suggesting the possible role of selected splice variants of the mu-opioid receptor gene Oprm1. This mouse model recapitulates our clinical observations and emphasizes the need to carefully monitor glucose levels when using high methadone doses, particularly intravenously, and the need for controlled clinical trials.     

The association between adherence to the Mediterranean diet and adiponectin levels among healthy adults: the ATTICA study

Adiponectin is thought to exert anti-inflammatory actions. The aim of the present work was to evaluate the association of long-term adherence to the Mediterranean diet with adiponectin levels, in a sample of cardiovascular disease-free adults. In a random sub-sample of “ATTICA” study, 532 men and women, serum adiponectin was measured. Among several sociodemographic, clinical and biological factors, adherence to the Mediterranean diet was assessed by a special diet score (MedDietSCore) that incorporated the inherent characteristics of this traditional diet. Unadjusted analysis revealed that participants who were in the highest tertile of the diet score had an average 41% higher adiponectin levels, as compared to those who were in the lowest tertile (P<.001). Multiadjusted data analysis showed that compared to the highest tertile of diet score, participants in the middle or the lowest one had an average 0.99±0.22 (P=.001) and 1.05±0.27 μg/ml (P=.001) lower adiponectin levels after adjusting for age, sex and various bioclinical factors. Adherence to the Mediterranean diet was associated with an increase on adiponectin levels. This finding may partially explain beneficial effects of this traditional healthy diet on the cardiovascular system.     

Feeding habits of the Atlantic bluefin tuna, Thunnus thynnus (L. 1758), in the central Mediterranean Sea (Strait of Messina)

The study of feeding habits of the Atlantic bluefin tuna was carried out in 123 specimens, ranging from 115 to 222 cm fork length (FL) and collected during spring seasons of 2010 and 2011 in the central Mediterranean Sea (Strait of Messina). The analysis of stomach contents allowed us to identify 91 taxa of prey items, mainly belonging to Teleostea (54), Cephalopoda (20) and Crustacea (13). The percentage of index of relative abundance (IRI) shows the highest values for the myctophid Hygophum benoiti (%IRI = 22.854) and the stomiid Chauliodus sloani (%IRI = 15.124), followed by the oegopsid squid Illex coindetii (%IRI = 14.316). The broad spectrum of prey items could suggest a generalist behavior of this predator, with several species that occasionally occurs in its diet. However, if prey are grouped into food categories, the importance of mesopelagic and benthopelagic fishes can be appreciated (54.41 % of %IRI). The assessment of the hypothetical foraging rhythm of the Atlantic bluefin tuna highlighted that its feeding activity is concentrated on diel migrating fauna during night and on larger preys upon daylight. The predation on the high-energetic food as mesopelagic and bathypelagic fishes during the pre-spawning and the spawning period may bring an energetic advantage in tuna metabolism and gonadal maturation     

Deficiency of mast cells in coronary artery endarterectomy of male patients with type 2 diabetes

Background

Increased fasting plasma glucose (FPG), which includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes, is a risk factor for arterial stiffness. While IFG is widely accepted as a cardiovascular risk factor, recent studies have argued that subjects with high-normal glucose level were characterized by a high incidence of cardiovascular disease. The purpose of this study is to investigate the relationship between FPG and arterial stiffness in non-diabetic healthy subjects.

Methods

We recruited 697 subjects who visited the health promotion center of a university hospital from May 2007 to August 2008. Age, sex, body mass index (BMI), resting heart rate, smoking habits, alcohol intake, exercise, blood pressure, medical history, FPG, lipid profile, high sensitivity C-reactive protein (hs-CRP), and Brachial-ankle pulse wave velocity (ba-PWV) were measured. We performed correlation and multiple linear regression analyses to divide the research subjects into quartiles: Q1(n = 172), 65 mg/dL ≤FPG < 84 mg/dL; Q2(n = 188), 84 mg/dL ≤FPG < 91 mg/dl; Q3(n = 199), 91 mg/dL ≤FPG < 100 mg/dL; Q4(n = 138), 100 mg/dL ≤FPG < 126 mg/dL.

Results

FPG has an independent, positive association with ba-PWV in non-diabetic subjects after correcting for confounding variables, including age, sex, BMI, blood pressure, resting heart rate, hs-CRP, lipid profile, and behavioral habits. The mean ba-PWV of the high-normal glucose group (Q3, 1384 cm/s) was higher than that of the low-normal glucose group (1303 ± 196 cm/s vs.1328 ± 167 cm/s, P < 0.05). The mean ba-PWV value in the IFG group (1469 ± 220 cm/s) was higher than that in the normoglycemic group (P < 0.05, respectively).

Conclusions

An increase in FPG, even within the normal range, was associated with aggravated arterial stiffness. Further research is needed to determine the glycemic target value for the prevention of arterial stiffness in clinical and public health settings.     

Structural and Compositional Changes in Erythrocyte Membrane of Obese Compared to Normal-Weight Adolescents

Unhealthy dietary habits are key determinants of obesity in adolescents. Assuming that dietary fat profile influences membrane lipid composition, the aim of this study was to analyze structural changes in the erythrocyte membrane of obese compared to normal-weight adolescents. The study was conducted in a group of 11 obese and 11 normal-weight adolescent subjects. The lipid profile, lipid peroxidation and acetylcholinesterase enzyme (AChE) activity were analyzed by conventional methods. The structural properties of reconstituted erythrocyte membrane were characterized by X-ray diffraction. Erythrocyte membrane from obese adolescents had a lipid profile characterized by a higher cholesterol/phospholipid ratio, an increase in saturated fatty acid and a decrease in monounsaturated and n-6 polyunsaturated fatty acid concentrations. Differences in lipid content were associated with changes in the structural properties of reconstituted membranes and the oxidative damage of erythrocyte membrane. The lower oxidative level shown in the obese group (0.15 ± 0.04 vs. 0.20 ± 0.06 nmol/mg for conjugated diene concentrations and 2.43 ± 0.25 vs. 2.83 ± 0.31 nmol/mg protein for malondialdehyde levels) was related to a lower unsaturation index. These changes in membrane structural properties were accompanied by a lower AChE activity (1.64 ± 0.13 vs. 1.91 ± 0.24 nmol AChE/[min mg protein]) in the obese group. The consequences of unhealthy dietary habits in adolescents are reflected in the membrane structural properties and may influence membrane-associated protein activities and functions.     

Blood hormone profiles,physiological variables,and behavioral criteria in Corriedale ewes fed different TMR moisture levels during thermal–humidity exposure

In this study, blood hormone profiles, physiological variables, and behavioral criteria in Corriedale ewes fed total mixed ration (TMR) at different moisture levels during thermal–humidity exposure were evaluated. Nine non-pregnant Corriedale ewes (ave. BW = 41 ± 3.5 kg) were individually fed diets based on maintenance requirements in metabolic crates. Ewes were assigned to three treatment groups according to a 3 × 3 Latin Square design for 3 periods of 21 days duration each (9 ewes per treatment). Treatments were TMR (CP (crude protein) = 16.1, TDN (total digestible nutrients) = 69.1%) moisture levels at 40, 50, and 60%. No differences were found in blood hormone profiles including cortisol (μg/dL), immunoglobulin G (mg/dL), triiodothyronine (ng/mL), thyroxin (μg/dL), growth hormone (ng/mL), prolactin (ng/mL), insulin (μU/mL), insulin-like growth factor 1 (ng/mL), aldostrone (ng/dL), antidiuretic hormone (pg/mL), and creatinine (mg/dL) among all treatment groups (p > 0.05). Measurements of physiological variables indicated that heart rate (number of beats/min) in the afternoon was higher in 50 and 60% TMR group than in the 40% group (p < 0.05). No differences were observed in respiratory rate (number/min), panting score, and fecal score among the groups (p > 0.05). The behavior criteria including urine excretion frequency (number/d), fecal excretion frequency (number/d), standing frequency (number/d), resting frequency (number/d), standing duration (min/d), and resting duration (min/d) showed no differences among the treatment groups (p > 0.05). Conclusions drawn indicate the minor impacts of TMR moisture levels up to 60% on behavioral criterions of Corriedale ewes during thermal–humidity exposure, but help smooth down the intensified heat stress conditions over physiological variables and endocrine system.     

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study

Background

To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs.

Methods

Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis.

Results

HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of ?0.73% (range, ?0.80 to ?0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months.

Conclusions

Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.

     

Effects of Dietary Supplementation of Zinc Oxide and Zinc Methionine on Layer Performance,Egg Quality,and Blood Serum Indices

The objective of this study was to evaluate the effectiveness of dietary zinc oxide (ZnO) and zinc methionine (Zn-Met) supplementation on layer performance, quality of egg, some blood constituents, and oxidative status in blood of laying hens. A total of 120 laying hens (Hisex Brown) 22-week-old were indiscriminately allotted into five groups of 24 hens with six replications (four birds/replicate). A complete randomized design experiment was performed including control (basal diet), two levels of ZnO (50 and 100 mg/kg basal diet), and two levels of Zn-Met (50 and 100 mg/kg basal diet) through 22 to 34 weeks of age. Supplementation of 100 mg of Zn-Met significantly (P = 0.001) increased feed intake compared to other treatment groups. The groups supplemented with 50 mg of ZnO and 100 mg of Zn-Met reported the significantly higher egg production rate (P = 0.002) and egg mass (P < 0.001) compared to other treated groups. All traits of egg quality were not statistically (P < 0.05 or 0.01) affected by ZnO or Zn-Met supplementation except shell thickness, Haugh unit score, and yolk to albumin ratio. Dietary supplementation of either ZnO or Zn-Met did not affect the oxidative parameters in serum except the activity of Cu-Zn-SOD. Serum triglyceride, total cholesterol, and LDL cholesterol (low-density lipoprotein) were significantly (P < 0.05) affected by Zn supplementation, while HDL cholesterol (high-density lipoprotein) did not affect. Compared to the control group, supplementation of ZnO or Zn-Met increased serum content of zinc with no differences among supplemental zinc doses. It could be concluded that dietary inorganic (ZnO) and organic (Zn-Met) supplemented up to 50 and 100 mg/kg, respectively, can be used as effective supplements to improve productivity of laying hens, serum zinc level, lipid profile (triglyceride and LDL cholesterol), and activity of Cu-Zn-SOD.     

Minimum Selenium Requirements Increase When Repleting Second-Generation Selenium-Deficient Rats but Are Not Further Altered by Vitamin E Deficiency

Second-generation selenium-deficient weanling rats fed graded levels of dietary Se were used (a) to study the impact of initial Se deficiency on dietary Se requirements; (b) to determine if further decreases in selenoperoxidase expression, especially glutathione peroxidase 4 (Gpx4), affect growth or gross disease; and (c) to examine the impact of vitamin E deficiency on biochemical and molecular biomarkers of Se status. Rats were fed a vitamin E-deficient and Se-deficient crystalline amino acid diet (3 ng Se/g diet) or that diet supplemented with 100 μg/g all-rac-α-tocopheryl acetate and/or 0, 0.02, 0.05, 0.075, 0.1, or 0.2 μg Se/g diet as Na₂SeO₃ for 28 days. Se-supplemented rats grew 6.91 g/day as compared to 2.17 and 3.87 g/day for vitamin E-deficient/Se-deficient and vitamin E-supplemented/Se-deficient groups, respectively. In Se-deficient rats, liver Se, plasma Gpx3, red blood cell Gpx1, liver Gpx1 and Gpx4 activities, and liver Gpx1 mRNA levels decreased to <1, <1, 21, 1.6, 49, and 11 %, respectively, of levels in rats fed 0.2 μg Se/g diet. For all biomarkers, ANOVA indicated significant effects of dietary Se, but no significant effects of vitamin E or vitamin E × Se interaction, showing that vitamin E deficiency, even in severely Se-deficient rat pups, does not result in compensatory changes in these biochemical and molecular biomarkers of selenoprotein expression. Se requirements determined in this study, however, were >50 % higher than in previous studies that started with Se-adequate rats, demonstrating that dietary Se requirements determined using initially Se-deficient animals can result in overestimation of Se requirements.