Blood pressure normalization by fixed perindopril/indapamide combination in hypertensive patients with or without associate metabolic syndrome: results of the OPTIMAX 2 study

The aim of the observational pharmaco-epidemiological study Optimax II was to seek whether the pre-existence of a metabolic syndrome (MS) defined by the NCEP-ATP III criteria impacts blood pressure (BP) control in hypertensive patients receiving a fixed perindopril/indapamide combination therapy. The primary objective of the study was to compare in patients with and without MS the rate of BP control defined as a systolic BP ≤140 mmHg and a diastolic BP ≤90 mmHg. Patients were prospectively included and the follow-up lasted 6 months. The study population consisted of 24,069 hypertensive patients (56% men; mean age 62 ± 11 years; 18% diabetics; mean BP at inclusion 162 ± 13/93 ± 9 mmHg). MS was found in 30.4% of the patients (n = 7322): 35.2% women and 20.1% men. Three therapeutic subgroups were constituted: Group A, previously untreated, received the combination therapy as initial treatment; Group B, previously treated but with unsatisfactory results and/or treatment intolerance, had its previous treatment switched to perindopril/indapamide; and Group C, previously treated, with good treatment tolerance but uncontrolled BP, received the study treatment in adjunction to the previous one. The normalization rate was 70.3% in group A, 68.4% in Group B, and 64.1% in Group C (p < 0.0001). The pre-existence of MS did not show any significant influence on these rates since BP lowering was −22.7 ± 13.7 (SBP) and −12.0 ± 10.0 mmHg (DBP) in patients without MS and −22.6 ± 13.3 (SBP) and −12.1 ± 9.7 (DBP) in those with MS. The results of this study show a significant effect of perindopril/indapamide treatment on systolic BP lowering, whatever the treatment status: initiation, switch, or adjunctive therapy, and independently from the presence or not of MS. This effect may be related to the specific vascular effect of the perindopril/indapamide combination, which has recently demonstrated in the ADVANCE trial its ability to reduce mortality, and cardiovascular and renal complications in diabetic patients

Duodenal enteroglucagonoma revealed by differential comparison of serum and tissue glucagon reactivity with Siemens' Double Glucagon Antibody and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report demonstrates that the differential immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>compared to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>allow for pathologic distinction of enteral versus pancreatic glucagonoma.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian man was diagnosed with a duodenal enteroglucagonoma following presentation with obstructive jaundice. He had a low serum glucagon level using Siemens' <it>Double Antibody Glucagon</it>, a clinical syndrome consistent with glucagon hypersecretion. A periampullary mass biopsy proved to be a neuroendocrine tumor, with positive immunohistochemical reactivity to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon</it>.</p> <p>Conclusions</p> <p>Differential comparison of the immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>and DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>discerns enteroglucagon from pancreatic glucagon.</p

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

OBJECTIVE: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. DESIGN: Multicentric prospective study. PATIENTS: A total of 162 patients with basal CT &lt;10 ng/l were included: 54 asymptomatic patients harboured noncysteine \u27rearranged during transfection\u27 (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. MEASUREMENT: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. RESULTS: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT &lt;5 ng/l had a positive Pg-stimulation test (Pg CT &gt;10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P &lt; 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. CONCLUSION: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test

A single-arm, open-label, intervention study to investigate the improvement of glucose tolerance after administration of the 5-aminolevulinic acid (5-ALA) in the patients with mitochondrial diabetes mellitus

Background: Mitochondrial diabetes mellitus (MDM) is characterized by maternal inheritance, progressive neurosensory deafness, insulin secretory disorder, and progressive microvascular complications. Mitochondria are critical organelles that provide energy in the form of adenosine triphosphate (ATP). An impairment of ATP production in pancreatic β cells is regarded as the main cause of the insulin secretory disorder in patients with MDM, and these patients require insulin replacement therapy early after the diagnosis. The amino acid 5-aminolevulinic acid (5-ALA), a precursor of heme metabolites, is a non-proteinogenic δ amino acid synthesized in mitochondria. An addition of ferrous iron to 5-ALA enhances heme biosynthesis and increases ATP production through an upregulation of the respiratory complex. Several studies have reported that the administration of 5-ALA and ferrous iron to existing treatment improved the glycemic control in both patients with prediabetes and those with type 2 diabetes mellitus. The additional administration of 5-ALA and ferrous iron to MDM patients on insulin therapy may improve their insulin secretory capacity and glycemic control by improving their mitochondrial function. The findings of this study are expected to provide new treatment options for MDM and improve the patients’ glycemic control and prognosis.Methods/design: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of treatment with 5-ALA plus sodium ferrous citrate (SFC) to patients with MDM on their glucose tolerance. A total of 5 patients with MDM will be administered 5-ALA/SFC (200 mg/d) for 24 weeks. We will perform a 75-g oral glucose tolerance test before and at 24 weeks after the start of this 5-ALA/SFC treatment to evaluate glucose-dependent insulin responses.Discussion: To the best of our knowledge, this study will be the first assessment of the effects of 5-ALA/SFC in patients with MDM. This study will obtain an evidence regarding the effectiveness and safety of 5-ALA/SFC for patients with MDM.Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN000040581) on July 1, 2020 and with the Japan Registry of Clinical Trials (jRCTs071200025) on August 3, 2020

Longitudinal association between medication adherence and glycaemic control in Type 2 diabetes

Aim Despite the widespread assumption that adherence drives glycaemic control, there is little published support for this in Type 2 diabetes. The study objective was to determine whether self‐reported medication adherence predicts future glycaemic control in Type 2 diabetes, after accounting for baseline control. Methods Medication adherence (4‐item Morisky scale), glycaemic control (HbA 1c %), and other variables were assessed in 287 adult primary care patients prescribed oral medication (40% also on insulin) for Type 2 diabetes. Glycaemic control was reassessed 6 months later. Regression analyses examined concurrent and future glycaemic control as a function of baseline medication adherence after adjustment for baseline glycaemia and other potential confounders. Results Only half of patients reported high adherence. Cross‐sectional adjusted analysis replicated prior reports of an adherence‐HbA 1c association ( P  = 0.011). Even after adjusting for baseline HbA 1c , each one‐point increase in baseline Morisky total score was associated with a 1.8 mmol/mol (or 0.16%) increase in HbA 1c measured 6 months later. Additionally, baseline endorsement of forgetting to take medication was associated with a 4.7 mmol/mol (or 0.43%) increase in 6‐month HbA 1c ( P  = 0.005). This effect persisted after adjusting for psychological distress and did not vary by key demographic and medical features. Conclusions Even after stringent adjustment for baseline glycaemic control, self‐reported adherence to diabetes medication predicts long‐term glycaemic control. The Morisky scale is an easy‐to‐use clinical tool to identify patients whose glycaemic control will subsequently worsen, regardless of age, gender and psychological distress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96675/1/dme12046.pd

Mitochondrial Diabetes in Children: Seek and You Will Find It

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants

Changing the Treatment Paradigm for Type 2 Diabetes

Based on the results of the U.K. Prospective Diabetes Study (UKPDS), “… treatment of type 2 diabetes [should] include aggressive efforts to lower blood glucose levels as close to normal as possible. …” This was the recommendation the American Diabetes Association promulgated based on the results of the UKPDS when published (1). The suggestion was soon adopted by official guidelines in every region of the world (2). They are generally consistent in recommending an A1C goal of <7.0%. However, the results of the UKPDS remained inconclusive with respect to cardiovascular (CV) complications because of a risk reduction that was only close to statistical significance (−16%, P = 0.052). In support of the UKPDS results, however, a recent meta-analysis of randomized trials in type 2 diabetes (3) calculated a 19% reduction in the incidence of any type of macrovascular event associated with improved long-term glycemic control. Moreover, a strong association between glycemic control and micro- and macrovascular disease has been highlighted in type 1 diabetic patients (4,5)

Drug Attitude and Adherence to Anti-Glaucoma Medication

PURPOSE: The purpose of this study is to assess patient attitudes towards anti-glaucoma medication and their association with adherence, visual quality of life, and personality traits. MATERIALS AND METHODS: One hundred and forty-seven glaucoma patients were enrolled this study. The participants were divided into 'pharmacophobic' and 'pharmacophilic' groups according to their scores on the Modified Glaucoma Drug Attitude Inventory (MG-DAI). To establish a correlation with patient drug attitude, each group had their subjective drug adherence, visual quality of life, and personality traits examined. For personality traits, the Myers-Briggs Type Indicator (MBTI) was used to sub-classify each group. RESULTS: Among the patients analyzed, 91 (72.80%) patients showed a 'pharmacophobic' attitude and 34 (27.20%) patients showed a 'pharmacophilic' attitude. The pharmacophobic group tended to have worse adherence than the pharmacophilic group. Personality dichotomies from the MBTI also showed different patterns for each group. CONCLUSION: In glaucoma patients, pharmacological adherence was influenced by their attitude towards drugs; an association might exist between drug attitude and underlying personality traits.ope

Lipoprotein (a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM

<p>Abstract</p> <p>Background</p> <p>Lipoprotein (a) (LP (a) is an independent cardiovascular risk factor that is not widely studied in people of sub-Saharan African origin. The aim of this report is to determine the frequency of occurrence of elevated Lp (a) and possible relationship with total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), C reactive protein (CRP) and serum uric acid (SUA).</p> <p>Methods</p> <p>This is a cross sectional study carried out in 200 Nigerian patients with type 2 DM and 100 sex and age matched healthy Controls aged between 32-86 years. We determined the frequency of occurrence of elevated Lp (a) levels in the study subjects and compared clinical and biochemical variables between type 2 diabetic patients and non-diabetic patients. Clinical and biochemical parameters were also compared between subjects with type 2 DM who had elevated LP (a) and normal LP (a) levels. Long term glycaemic control using glycosylated haemoglobin was determined and compared in the study subjects. Test statistics used include chi square, correlation coefficient analysis and Student's t test.</p> <p>Results</p> <p>The mean Lp(a) concentration differed significantly between type 2 diabetic patients and the Control subjects (18.7 (5.8) mg/dl vs 23 (6.8) mg/dl, 0.00001). Similarly, the prevalence of high LP (a) levels in type 2 DM patients was significantly higher than that of the Control subjects (12.5% vs 4%, p-0.019). The mean levels of the lipid profile parameters (TCHOL, LDL-C, TG, LDL/HDL) and CRP were significantly higher in DM patients than in the Control subjects. The mean LP (a) levels were comparable in both sexes and in DM subjects with and without hypertension. TG was the only parameter that differed significantly between subjects with elevated Lp (a) levels and those with normal Lp (a) levels. There was a significant positive correlation (r) between Lp(a) levels and TG, LDL-C. TCHOL, LDL/HDL and uric acid. No association was found between Lp(a) and clinical parameters such as age and anthropometric indices.</p> <p>Conclusion</p> <p>We have showed that Lp (a), CRP and other CVS risk factors cluster more in patients with DM than non DM patients. Serum Lp (a) levels are not associated with anthropometric and glycaemic indices.</p