Diet-treated Patients Research Articles

Differential placental ceramide levels during gestational diabetes mellitus (GDM)

BackgroundGestational diabetes mellitus (GDM) is associated with important factors that influence fetal development. Sphingolipids are known to be associated with the development of diabetes. Our objective was to examine ceramide, a key sphingolipid, hyperosmolarity, and apoptosis in placentas from GDM patients treated with insulin or diet.MethodsCeramide levels were assessed in placental tissues using immunohistochemistry. Immunoblot was performed to quantify serine palmitoyltransferase (SPT), the rate-limiting enzyme in ceramide biosynthesis, NFAT5, SMIT, AR, caspase 3 and the X-linked inhibitor of apoptosis. Trophoblast cells were treated with insulin or ceramide and assessments for mitochondrial respiration, caspase 3 and XIAP were also performed.ResultsImmunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Nuclear SPT was upregulated only in the insulin-treated GDM placenta when compared to controls. Nuclear NFAT5 was also increased in the GDM placenta. Active caspase 3 was elevated in placentas from both insulin- and diet-treated GDM patients. Mitochondrial respiration was decreased in trophoblasts treated with ceramide. Active caspase was not changed while XIAP protein was increased in trophoblasts treated with ceramide.ConclusionsOur findings confirm the presence of ceramide in the human placenta of control and GDM patients. Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration.

Association of Simvastatin and Hyperlipidemia With Periodontal Status and Bone Metabolism Markers

The objective of this study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and specific bone activity biomarkers. This cross-sectional and analytic study includes 73 patients divided into three groups: 1) simvastatin-treated patients with hyperlipidemia (n = 29); 2) patients with hyperlipidemia treated by diet alone (n = 28); and 3) normolipidemic patients (controls, n = 16). The periodontal clinical variables of all participants were gathered, a blood sample was drawn from each to determine the lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), serum levels of acute-phase reactants (C-reactive protein), erythrocyte sedimentation rate, and bone metabolism markers (osteoprotegerin [OPG], osteocalcin, procollagen type I N-terminal propeptide, and C-terminal telopeptide of type I collagen). The mean ESR was higher in the diet-treated patients with hyperlipidemia than in the normolipidemic controls (P = 0.04). Serum OPG concentrations were significantly higher in the simvastatin-treated patients with hyperlipidemia than in the diet-treated patients with hyperlipidemia (P = 0.05). Multivariable linear regression analysis adjusted for age, sex, tobacco, and alcohol revealed that, compared with the normolipidemic patients, the simvastatin-treated patients with hyperlipidemia showed a mean reduction of 0.8 mm (95% confidence interval = -1.5 to 0.0, P = 0.05) in clinical attachment loss. Within the limits of this study, the findings suggest that the intake of simvastatin is associated with increasing serum OPG concentrations, and this could have a protective effect against bone breakdown and periodontal attachment loss. The baseline systemic inflammatory state of patients with hyperlipidemia is indicated by their increased erythrocyte sedimentation rate.

Predicting the Need for Medical Therapy in Patients with Mild Gestational Diabetes

The enforcement of a one-step gestational diabetes mellitus (GDM) diagnosis would capture more patients with milder forms of glucose intolerance thereby increasing the incidence. We propose to identify characteristics predicting the need for medical therapy in such patients. Retrospective chart review of patients with mild GDM, defined as a fasting plasma glucose (FPG) < 95 mg/dL on the 3-hour 100-g oral glucose tolerance test (OGTT). Patients requiring medical therapy for glucose control were compared with diet-controlled patients. A predictive model was constructed with variables of significance. Included were 143 patients requiring medical therapy and 224 diet-treated patients. Mean FPG on 3-hour OGTT, prepregnancy body mass index (BMI), and BMI at 26 to 30 weeks were all significantly higher in patients requiring therapy. Combining several variables produced a predictive model with 76% sensitivity, 52% specificity, 48% positive predictive value, and 78% negative predictive value. Antenatal factors (alone or in combination) do not allow for prediction of the possible need for therapy in mild GDM patients.

Self‐monitoring of blood glucose in Type 2 diabetes: cross‐sectional analyses in 1993, 1999 and 2009

To characterize the numbers of reagent strips dispensed for self-monitoring of blood glucose to patients with Type 2 diabetes in Tayside, Scotland, in 1993, 1999 and 2009. A diabetes clinical information system in Tayside, record-linked to electronic dispensed prescribing records, was used to collate all dispensed prescribing records for three cross-sectional samples of patients with Type 2 diabetes in 1993 (n = 5728), 1999 (n = 8109) and at 1 January 2009 (n = 16,450). The numbers of reagent strips dispensed during the relevant calendar year were calculated and patients stratified by treatment. We also explored whether age, sex or material and social deprivation were associated with whether a patient received strips. Proportions of people who received self-monitoring reagent strips increased from 15.5% in 1993, to 24.2% in 1999 to 29.8% in 2009, as did numbers of strips dispensed. While the proportion of diet-treated patients who received reagent strips was still very low in 2009 (5.6%), the proportion among those treated with oral agents tripled from 9.4 to 27.4% between 1993 and 2009. Over 90% of patients treated with insulin received reagent strips and, among non-insulin-treated patients, this was more common among women, younger people and less deprived groups. The numbers of reagent strips dispensed for self-monitoring of blood glucose has increased and almost all insulin-treated patients receive strips. While few diet-treated patients receive strips, they are more extensively dispensed to those treated with oral agents. Given that self-monitoring of blood glucose is no longer routinely recommended in non-insulin treated patients, strategies to reduce unnecessary dispensing of reagent strips are needed.

A comparison of the effect of glitazones on serum sialic acid in patients with type 2 diabetes

Although management of hyperglycaemia represents one of the principal treatment goals of diabetes therapy, the high incidence of cardiovascular (CV) complications in diabetes also needs effective management. Therefore, the present study was designed to determine and compare the effect of glitazones on serum sialic acid (SSA), a known risk marker for CV disease, along with fasting plasma glucose (FPG), glycohaemoglobin (HbA1-c) and blood lipids, in overweight, previously only diet-treated patients with type 2 diabetes (n=60). The study was conducted for a period of 12 months. Significant improvement in FPG and HbA1-c were shown by both rosiglitazone (p<0.003 and p<0.001, respectively) and pioglitazone (p<0.005 and p<0.001, respectively), compared with baseline, and pioglitazone showed greater beneficial effects on other parameters monitored, significantly reducing total cholesterol (TC) (p≤0.05). Both the drugs showed a decrease in SSA and no significant differences were observed between the groups. However, the decrease was significant only in the pioglitazone-treated group at month 12 (p≤0.05), compared with baseline. A significant decrease in SSA by pioglitazone indicates its greater cardioprotective effect compared with rosiglitazone.

The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes

To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes. The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009. Subjects were randomly assigned to receive either myoinositol supplementation (4 g daily) plus folic acid (400 μg daily)-the study group-or folic acid only (400 μg daily)-the control group. Both groups received the same diet prescription. Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment. There were 69 evaluable patients, 24 in the study group and 45 in the control group. Fasting glucose and insulin, and consequently homeostasis model assessment of insulin resistance, decreased in both groups (50% in the study group vs. 29% in the control group), but the decline in the study group was significantly greater than that in the control group (P = 0.0001). Adiponectin increased in the myoinositol group while it decreased in the control group (P = 0.009). Myoinositol improves insulin resistance in patients with gestational diabetes.

Determinants of an Optimal Response to Pioglitazone in Terms of HDL-Cholesterol

The effect of pioglitazone on high-density lipoprotein cholesterol (HDL-C) has been attracting attention. However, there are limited data on the characteristics of patients who are likely to respond to pioglitazone in terms of the improvement in HDL-C levels (lipid responders). In the present study, the characteristics of lipid responders were investigated. Five hundred and sixty-three patients with type 2 diabetes who started pioglitazone treatment were followed for six months. They were divided into two groups according to the response to pioglitazone. Subjects whose HDL-C levels increased by 10% or more from the baseline were defined as lipid responders. The odds ratios (OR) for becoming lipid responders were calculated using logistic regression. Significant patients' characteristics of lipid responders were age, HbA1c, HDL-C and low-density lipoprotein cholesterol (LDL-C), yielding adjusted ORs of 0.76 [95% confidence interval (CI)=0.61-0.93] for an increment of 10 years, 0.79 (95% CI=0.66-0.95) for an increment of 1%, 0.83 (95% CI=0.72-0.96) for an increment of 10 mg/dL and 0.93 (95% CI=0.87-1.00) for an increment of 10 mg/dL, respectively. Patients with sulfonylurea treatment and those with both sulfonylurea and metformin treatment were less likely to become lipid responders than diet-treated patients with ORs of 0.32 (95% CI=0.15-0.69) and 0.41 (95% CI=0.19-0.87), respectively. Pioglitazone could be beneficial especially for patients with young age, low HbA1c, low HDL-C or low LDL-C levels at baseline in terms of the improvement in HDL-C levels. Use of sulfonylureas at baseline could attenuate the effect of pioglitazone on HDL-C.

Blood phenylalanine control in phenylketonuria: a survey of 10 European centres

Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet. A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in 10 European centres. Centres experienced in the management of PKU from Belgium, Denmark, Germany, Italy, The Netherlands, Norway, Poland, Spain, Turkey and the United Kingdom provided retrospective audit data of all patients with PKU treated by diet over a 1-year period. Standard questions were used to collect median data on blood Phe concentrations, percentage of blood Phe concentrations below upper target reference ranges and frequency of blood Phe sampling. Data from 1921 patients on dietary management were included. Blood Phe concentrations were well controlled and comparable across centres in the early years of life. The percentages of blood Phe concentrations meeting each centre's local and national target ranges were 88% in children aged up to 1 year, 74% for 1-10 years, 89% for 11-16 years and 65% for adults (>16 years). The frequency of home blood sampling, compared with local and national recommendations for monitoring Phe concentrations, appeared to decline with age (from approximately 100% in infancy to 83% in teenagers and 55% in adults). Although blood Phe control generally deteriorated with age, some improvement was observed in adolescent years across the 10 European centres. The blood Phe control achieved seemed comparable in many of the European centres irrespective of different dietary treatments or national policies.

Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus.

To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study. After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d.,effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake. Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of -1.8 microU ml(-1), 95% confidence interval (CI) -7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean C(max) and AUC(tau) (95% CI) and median t(max) (range) in this patient population were 180 ng ml(-1) (125, 260), 581 ng.h ml(-1) (422, 800) and 3.0 h (0.67, 4.3), respectively. The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes.

Self blood glucose monitoring in type 2 diabetes. A financial impact analysis based on UK primary care

UK consensus guidelines recommend limited use of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes using diet and exercise, metformin and/or a glitazone. This analysis quantifies the usage of and costs associated with SMBG in type 2 diabetes according to treatment regimen. Prevalence data for diabetes were assessed using UK Quality and Outcomes Framework returns for 2006/2007. Data on current SMBG prescribing expenditure were extracted from UK Prescription Pricing Agency Data for 2007. Prescribing data were extracted from the records of 40,651 patients with diabetes on the IMS Disease Analyzer (MediPlus) database. These were combined to arrive at mean usage and expenditure data per patient, broken down by treatment type. The analysis assumes that it is appropriate to use patients' treatment regimen alone to compare the frequency of SMBG in clinical practice with the frequency recommended in treatment guidelines; it does not take into account other valid reasons for SMBG. Mean national expenditure on SMBG was 73.64 pound sterling per patient per year. Estimated mean weekly test strip usage by treatment was 2.5 (diet), 2.6 (glitazone monotherapy), 3.1 (metformin monotherapy) and 3.5 (sulphonylurea monotherapy). Combination oral therapy ranged from 3.3 to 4.1. Mean annual expenditure in patients with an identified treatment type was 62.06 pound sterling per patient, ranging from 9.83 pound sterling for diet-treated patients to 37.87 pound sterling for those on triple therapy, with insulin-treated patients incurring costs 3-5 times higher. Based on the assumptions that the treatment regimen is the sole factor in determining the appropriate level of SMBG frequency, this study demonstrates that the use of SMBG exceeds current guidelines in certain treatment groups. The study estimates that the potential savings of up to 17 million pound sterling could be made each year if guidelines were followed more closely. There is a need for further research into SMBG use in patients with type 2 diabetes.

Intragastric Balloon or Diet Alone? A Retrospective Evaluation

Very few studies have reported results of the BioEnterics Intragastric Balloon (BIB) at > or =12 months follow-up. The aim of this study is the retrospective evaluation of the results of BIB placement compared to diet regimen alone. From January 2005 to June 2006, 130 outpatients underwent a structured diet plan with simple behavioral modification at our institutions. Controls (n = 130) were selected from the charts of patients who, during the same period, underwent BIB treatment. Patients in the outpatient group were given a structured balanced diet with a caloric intake between 1,000 and 1,200. The approximate macronutrient distribution, according the "Mediterranean diet," was 25% protein (at least 60 g/day), 20-25% lipids, and 50-55% carbohydrates. In the BIB group, patients received generic counseling for eating behavior. In both groups, we considered weight loss parameters (kilograms, percentage of excess weight loss [%EWL], body mass index [BMI], percentage of excess BMI loss [%EBL]) at 6 and 24 months from baseline and comorbidities at baseline and after 24 months. Results are expressed as mean+/-standard deviation. Statistical analysis was done by Student's t-test and chi (2)-test or Fisher's exact test. p < .05 was considered significant. At the time of BIB removal (6 months), significantly better results in terms of weight loss in kilograms (16.7 +/- 4.7 vs. 6.6 +/- 2.6; p < 0.01), BMI (35.4 +/- 11.2 vs. 38.9 +/- 12.1; p < 0.01), %EBL (38.5 +/- 16.1 Vs 18.6 +/- 14.3; p < 0.01), and %EWL (33.9 +/- 18 vs. 24.3 +/- 17.0; p < 0.01) were observed in patients treated by intragastric balloon as compared to diet-treated patients. At 24 months from baseline, patient dropout was 1/130 (0.7%) and 25/130 (19.2%) in the BIB and diet groups, respectively (p < 0.001). At this time, patients treated with intragastric balloon have tended to regain weight, whereas diet-treated patients have already regained most of lost weight. Although the strength of this study may be limited by its retrospective design, the results indicate that, in the short-to-medium term, BIB is significantly superior to diet in terms of weight loss.

The impact of diabetes on prescription drug costs: the population-based Turin study

The aim of our study was to compare prescription drug costs in diabetic and non-diabetic individuals in a large population-based Italian cohort covered by the National Health System. We identified diabetic residents in Turin on 31 July 2003 through multiple independent data sources (diabetes registry, hospital discharges and prescriptions data sources). All prescriptions registered in the 12 month period 1 August 2003 to 31 July 2004 were examined to compare prevalence of treatment and costs in diabetic (n = 33,797) and non-diabetic individuals (n = 863,876). A log-linear model was employed to estimate age- and sex-adjusted ratios of costs. Costs per person per year were 830.90euros in diabetic patients and 182.80euros in non-diabetic individuals (age- and sex-adjusted rate ratio 2.8, 95% CI 2.7-2.9). Diabetes treatment accounted for 18.5% of the total cost. Compared with non-diabetic individuals, the excess of expenditure was particularly high in diabetic patients aged <45 years (rate ratio 9.3), in those with type 1 diabetes (rate ratio 7.7) and in insulin users (rate ratio 4.8). The cost of diet-treated patients was similar to those treated with oral drugs. Diabetes was associated with an increased prevalence of treatment for most drug categories; one-third of the diabetic cohort received ACE inhibitors, anti-thrombotic drugs and statins. This population-based study shows that diabetes has a great impact on prescription drug costs, independently of main confounders, particularly in insulin-treated patients, suggesting that a wide range of comorbidities affect their health. Costs are expected to further increase if the transferability of knowledge provided by evidence-based guidelines on diabetic patients is completed over the coming years.

Clinical Efficacy of Two Hypocaloric Diets That Vary in Overweight Patients With Type 2 Diabetes

Approximately 80% of patients with type 2 diabetes are overweight/obese (1), and weight loss is the mainstay of treatment for these individuals. However, there is growing controversy as to whether reduced-fat or reduced-carbohydrate diets are best suited for this purpose, and results (2–8) in nondiabetic subjects suggest that lower carbohydrate diets are similarly or more efficacious in improving weight, triglycerides, and HDL cholesterol. There are no published randomized studies evaluating the role of dietary macronutrients with respect to weight loss and cardiovascular risk improvement in patients with type 2 diabetes. Thus, we randomized diet-treated patients with type 2 diabetes to hypocaloric diets, moderately restricted in either carbohydrate or fat, to determine whether weight loss or metabolic improvement differed as a function of macronutrient composition. A total of 29 patients with diet-treated type 2 diabetes were recruited from the San Francisco Bay area. All subjects gave written informed consent. Inclusion criteria included BMI 27–36 kg/m2, fasting plasma glucose concentration 7.2–8.3 mmol/l, no use of antihyperglycemic medications, and stable weight for 3 months. Subjects on anti-hypertensive or cholesterol-lowering drugs or aspirin were allowed to continue their medications. Insulin-mediated glucose uptake was quantified by a modification (9) of the insulin suppression test as originally described (10) and validated (11). In this test, a 180-min infusion of somatostatin (0.27 μg/m2 per min), insulin (25 mU/m2 per min), …

The SPINK gene family and celiac disease susceptibility.

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n = 15) and diet-treated patients (n = 31) and controls (n = 16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-007-0199-5) contains supplementary material, which is available to authorized users.

Association of diabetes‐related emotional distress with diabetes treatment in primary care patients with Type 2 diabetes

To characterize the determinants of diabetes-related emotional distress by treatment modality (diet only, oral medication only, or insulin). A total of 815 primary care patients with Type 2 diabetes completed the Problem Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a diabetes clinical research database and used linear regression models to assess the associations of treatment with PAID score. PAID scores were significantly higher among insulin-treated (24.6) compared with oral-treated (17.8, P < 0.001) or diet-treated patients (14.7, P < 0.001), but not different between oral- vs. diet-treated patients (P = 0.2). Group scores remained similar, but the statistical significance of their differences was reduced and ultimately eliminated after sequential adjustment for diabetes severity, HbA(1c), body mass index, regimen adherence, and self-blood-glucose monitoring. Insulin-treated patients reported significantly higher distress than oral- or diet-treated patients on 16 of 20 PAID items. 'Worrying about the future' and 'guilt/anxiety when ... off track with diabetes' were the top two serious problems (PAID >or= 5) in all treatment groups. Not accepting diabetes diagnosis was a top concern for oral- and diet-treated patients, and unclear management goals distressed diet-treated patients. Primary care patients treated with insulin reported higher diabetes-related emotional distress compared with oral- or diet-treated patients. Greater distress was largely explained by greater disease severity and self-care burdens. To improve diabetes-specific quality of life, clinicians should address patients' sense of worry and guilt, uncertain acceptance of diabetes diagnosis, and unclear treatment goals.

The characteristics of glycemic profile in obese, diet-treated GDM patients

The characteristics of glycemic profile in obese, diet-treated GDM patients

Risk of death or acute myocardial infarction 10 years after coronary artery bypass surgery in relation to type of diabetes

The aim of this study was to assess the long-term risk of death or acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) compared with that in patients without DM after coronary artery bypass grafting (CABG). National registers were used to record death or AMI occurring in 6727 patients who had CABG during 1980 to 1995. Diabetes mellitus in 856 patients (13%) was classified as type 1 (6%) or type 2 treated with insulin (29%), oral drugs (46%), or diet (19%). The risk of death < or = 30 days of the operation was increased in patients with insulin-treated type 2 DM (odds ratio [OR] 4.6, 95% CI 2.5-8.4) and in those on oral antidiabetic drugs (OR 2.0, 95% CI 1.0-3.8), but not in diet-treated diabetic patients, compared with that in patients without diabetes. At 10 years, the relative risk of death or having an AMI was 1.8 (95% CI 1.5-2.2) in insulin-treated patients and 1.4 (95% CI 1.2-1.7) in patients on oral drugs. No increased risk of late death or AMI was observed in diet-treated patients with diabetes compared with patients without diabetes. Survival at 10 years without an AMI was 40% in insulin-treated type 2 diabetic patients, 48% if on oral drugs, and 59% if diet managed, compared with 66% in nondiabetic patients. Type 2 DM requiring insulin treatment or oral antidiabetic drugs is associated with an increased early and long-term risk of death or AMI after CABG, whereas diet-treated patients have a risk similar to that in patients without diabetes.

Greater use of insulin by southern European compared with Anglo-Celt patients with type 2 diabetes: the Fremantle Diabetes Study

To investigate the relationship between blood glucose-lowering therapy, glycaemia and ethnicity in urban Australians with type 2 diabetes. Prospective observational community-based study of diabetes care, control and complications. We analysed cross-sectional data from 1057 patients, 238 from a southern European (SE) migrant background and 819 Anglo-Celts (AC). Follow-up data were available for 539 patients (113 SE, 426 AC) who had annual reviews over 4 years. The SE patients were of similar age to the AC patients but had longer diabetes duration, were less fluent in English and had less formal education. After adjustment for diabetes duration, glycosylated haemoglobin and glutamic acid decarboxylase antibody positivity in a logistic regression model, insulin use at study entry was approximately twice as frequent amongst SE as AC patients (odds ratio (95% confidence interval); 1.90 (1.20-3.02)). In the prospective arm, progression to insulin increased in both groups, from 18.0% at baseline to 22.1% at 4 years in SE and from 7.1% to 14.4% in AC patients. beta-cell function (%B) and insulin sensitivity (%S) using the homoeostasis model assessment in a subset of diet-treated patients at baseline showed that SE ethnicity was associated with lower %B and greater %S than in the AC group. SE patients with early non-antibody-mediated beta-cell failure progress to insulin requirement within the first 4-5 years of type 2 diabetes. This could reflect either a longer period of undiagnosed diabetes or a more rapid loss of beta-cell function after diagnosis.

Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients.

Celiac disease (CD), or gluten sensitivity, is considered to be a state of heightened immunologic responsiveness to ingested gluten proteins in genetically predisposed individuals. The gastrointestinal manifestation suggests a severe enteropathy of the small intestine with malabsorption, steatorrhea, and weight loss because of a deranged mucosal immune response. Neurologic complications occur, especially epilepsy, possibly associated with occipital calcifications or folate deficiency and cerebellar ataxia. There have been reports of brain white-matter lesions as an extraintestinal manifestation in Crohn disease and ulcerative colitis but not in CD. In this study, 75 diet-treated mainly pediatric patients with biopsy-proven CD underwent prospectively clinical neurologic examinations, laboratory investigations, electroencephalography, computed tomography, and magnetic resonance imaging. The age range was 2.8 to 24.2 years with a mean of 11.6 years. The mean period of gluten exposure was 2.4 years. Ten patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development. No folate deficiency was found. The hippocampal regions showed no abnormalities. Computed tomography did not reveal any cerebral calcifications, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%). There was no correlation between these lesions and dietary compliance or neurologic or electroencephalographic abnormalities. The mean gluten exposure time of these patients was slightly increased (not significant). Focal white-matter lesions in the brain may represent an extraintestinal manifestation of CD. They may be ischemic in origin as a result of a vasculitis or caused by inflammatory demyelination. They seem to be more typical of pediatric CD than cerebral calcifications. Their prognostic value is unclear and needs to be elucidated in additional studies. CD should be suggested as a differential diagnosis in children with unclear white-matter lesions even without intestinal symptoms.

Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features

Objectives. Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. Methods. Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). Results. The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 ± 39 mg/dL to 174 ± 42 mg/dL), total testosterone (422 ± 122 ng/dL to 360 ± 128 ng/dL), and free androgen index (36.3% ± 18.9% to 29.3% ± 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 ± 5.2 ng/mL and 8.5 ± 7.7 ng/mL, respectively, for the entire sample ( P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 ± 3.9 ng/mL and 6.4 ± 4.1 ng/mL ( P = 0.10). The mean proliferation index was 7.4 ± 7.8 for the historic controls versus 5.0 ± 4.9 for the diet-treated patients ( P = 0.05). The distribution of the apoptotic indexes differed significantly ( P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet ( P = 0.049 and P = 0.017, respectively). Conclusions. These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.