Overt Diabetes Mellitus Research Articles

Relation of the metabolic syndrome with proarrhythmogenic electrocardiographic parameters in patients without overt diabetes

Objectives We aimed to observe the relationship of the metabolic syndrome and proarrythmogenic ECG parameters and to evaluate a possible correlation of these parameters to the metabolic syndrome score in patients without overt diabetes mellitus.Methods The study population consisted of 142 patients with the metabolic syndrome and 170 age-and gender-matched control subjects. In the ECG recordings, resting heart rate, QRS duration, corrected QT duration and corrected QT dispersion were measured. Patients were classifi ed into three groups based on number of fulfi lled metabolic syndrome criteria: group 1 (three metabolic syndrome criteria), group 2 (four metabolic syndrome criteria) and group 3 (fi ve metabolic syndrome criteria).Results Patients with the metabolic syndrome had a higher increased resting heart rate, QTcd, prolonged QRS and QTc duration. Resting heart rate increases signifi cantly parallel to the increase in the metabolic syndrome score across the groups, whilst QRS duration remained unchanged. QTc duration and QTc dispersion were signifi cantly higher in groups 2 and 3 when compared to group 1. However, no signifi cant diff erences were observed between groups 2 and 3.Conclusion We demonstrated that the metabolic syndrome and its score related with increased resting heart rate and prolonged repolarization durations in patiens without overt diabetes mellitus. These pro arrhythmogenic parameters could be used in the development of risk stratifi cation schemes for sudden cardiac death in patients with the metabolic syndrome.

Prognostic Significance of Unrecognized Myocardial Infarction Detected with MR Imaging in Patients with Impaired Fasting Glucose Compared with Those with Diabetes

To investigate whether the presence of myocardial infarction (MI) detected with late gadolinium-enhanced magnetic resonance (MR) imaging is an independent predictor of major adverse cardiac events (MACEs) in patients with impaired fasting glucose (IFG) and those with overt diabetes mellitus (DM). Institutional review board approval was obtained for this study, and all subjects provided written informed consent. Late gadolinium-enhanced and cine MR imaging were performed in 190 patients with IFG and 160 patients with DM without known previous MI to evaluate the presence and extent of late gadolinium enhancement as well as global and regional left ventricular function. MACEs were defined as cardiac death, MI, unstable angina, heart failure, and ventricular arrhythmia. The Cox proportional hazards model was used to investigate the relationship between clinical and MR imaging variables and MACEs. Follow-up information was obtained in 181 of the 190 patients with IFG (95%) and 151 of the 160 patients with DM (94%). MACEs were observed in 15 of the 181 patients with IFG (8.3%) and 24 of the 151 with DM (15.9%). Late gadolinium enhancement was an independent predictor for MACE in both the IFG group (adjusted hazard ratio, 5.186; P = .003) and DM group (adjusted hazard ratio, 3.229; P = .015). MACE-free survival was significantly higher in patients with IFG than in those with DM (P = .019, log-rank test). However, the MACE-free survival curve for patients with IFG and late gadolinium enhancement was similar to that for patients with DM and late gadolinium enhancement (P = .735). The presence of MI detected with late gadolinium-enhanced MR imaging is the strongest multivariable predictor of adverse cardiac events in patients with IFG. Late gadolinium-enhanced MR imaging may help identify a subpopulation of subjects in the prediabetic stage who may benefit from more intensive treatments.

Childhood onset diabetes posttransplant in a girl with TCF2 mutation

Heterozygous mutations of TCF2 (transcription factor 2) have been associated with maturity onset diabetes of the young, renal malformations, hyperuricemia, and occasionally internal genital malformations in female. We report a female patient with bilateral renal hypodysplasia and de novo heterozygous TCF2 gene mutation. At the age of 9 yr, she developed transient ketoacidosis immediately posttransplant, temporarily requiring insulin. During glucocorticoid tapering, impaired glucose tolerance persisted and overt insulin-dependent diabetes mellitus developed 1 yr later. Pathogenic factors which might have played a role in the acceleration of diabetes were (i) switch from cyclosporine to tacrolimus, (ii) weight excess, and (iii) cytomegalovirus infection. TCF2 analysis might, therefore, be of interest in patients with congenital abnormalities of the kidney and the urinary tract in order to improve posttransplant management in terms of steroid and tacrolimus exposure.

Re: Microalbuminuria in Normal Korean Children

Re: Microalbuminuria in Normal Korean Children

Nalidixic acid and diabetic ketoacidosis

Sir, Nalidixic acid as the first quinolone was isolated as a by-product of the synthesis of chloroquine. It has been available for the treatment of urinary tract infections for many years.[1] We present here the report of a 13-year-old girl who was referred to the toxicologic emergency department of Baharloo Hospital by a general physician from his office because of seizure and decrease in consciousness. Her seizure was tonic clonic and did not repeat more than one time during hospitalization. There was no history of previous disease. She was diagnosed as diabetic ketoacidosis (DKA) based on her laboratory test results on admission to the hospital, and thus the treatment was started. She was completely cured without any signs and symptoms of diabetes and DKA, 24 h after admission. Her drug history showed nalidixic acid overdosage. Her first complaints were agitation, jerking, and spasm in her upper limbs, along with low consciousness that was diagnosed as seizure by a general physician and cured by administration of diazepam in his office (her seizure might be due to nalidixic acid, but the other etiologic factors such as severe acidosis and electrolyte disturbances might not be ruled out). Her initial vital signs and lab tests on hospital admission are shown in Table 1. Neurological examination was intact except mild agitation and confusion. Fever was not detected. In urine analysis, ketones were large and glucose was 1+. Urine culture was sterile. Arterial blood gas (ABG) was reported as severe acidosis. Chest X-ray was normal. By taking history and performing lab tests, the other etiologies of metabolic acidosis, like renal failure, alcohol drinking, starvation and consumption of other toxins, were ruled out. Table 1 Initial vital signs and lab tests on hospital admission She was diagnosed as DKA and treatment was given with insulin (10 U regular status + 5 U/h), normal saline (2000 mL for 3 h), and potassium (10 mL KCl 15% in 1 L of serum). After continuation of treatment, her blood sugar finally reached 111 mg/dL and ABG became normal [Table 2]. She had a family history of diabetes mellitus as her brother was a diabetic, but there was no history of atopic or epilepsy. Ten empty packets of nalidixic acid (ingested with a suicidal intention) were found near her bed, which was confirmed by history taking after the patient showed clinical improvement. Twenty-four hours after treatment, the patient was completely cured without any symptoms and signs of diabetes and DKA. Table 2 Arterial blood gas and arterial blood glucose data and treatment There are reports of glycosuria[2–4] and hyperglycemia, convulsions, in overdosage of nalidixic acidor even therapeutic dose of nalidixic acid.[5] There are also reports of metabolic acidosis in overdosage[6–9] or therapeutic dose of nalidixic acid.[1,10] To our knowledge, till date there has been no report of DKA following overdosage of nalidixic acid. DKA may be the initial symptom complex that leads to a diagnosis of type 1 DM, but more frequently it occurs in individuals with established diabetes. Nausea and vomiting are often prominent, and their presence in an individual with diabetes warrants laboratory evaluation for DKA[11] Drugs can also be a precipitating factor. There are reports of hyperglycemia, convulsions,[1] and glycosuria in overdosage of nalidixic acid.[2–4] As far as our patient is concerned, she had a positive family history of diabetes mellitus and this presentation may be due to the window period of diabetes mellitus. So, there is a need to follow-up the patient as she could develop overt diabetes mellitus. However, more precautions need to be taken while prescribing nalidixic acid for high-risk patients for diabetes mellitus. As this communication is the first report of its kind, it should encourage aggressive pharmacovigilance in future.

245: Can a hemoglobin A1C value obtained in the first half of pregnancy in women with gestational diabetes mellitus predict the postpartum diagnosis of overt diabetes mellitus?

245: Can a hemoglobin A1C value obtained in the first half of pregnancy in women with gestational diabetes mellitus predict the postpartum diagnosis of overt diabetes mellitus?

Interaction Between Post-Transplant Diabetes Mellitus and Regulatory T Cell Phenotype

Abstract 3039 Background:Post-transplant diabetes mellitus (PTDM) is a common complication that is associated with numerous medical conditions affecting the long-term survival of patients undergoing allogeneic hematopoietic cell transplantation (HCT). Immune dysregulation manifested by chronic low-grade inflammation and decreased frequencies of regulatory T cells (Tregs) in visceral adipose tissue are key determinants in the transition from insulin resistance to overt diabetes mellitus. We tested the hypothesis that new-onset PTDM is associated with measurable changes in cellular immunity and Treg subsets during HCT. Methods:Patients aged ≥ 18 years undergoing HCT who were simultaneously enrolled in two independent clinical trials examining either PTDM or tissue-specific Tregs were included in this analysis (N= 36). Fasting glucose levels were assessed weekly until day +100. New-onset PTDM was defined as a fasting glucose ≥ 126 mg/dL or random glucose ≥ 200 mg/dL after HCT in an individual without history of diabetes mellitus. Tregs were identified using polychromatic flow cytometry by the following phenotype: CD45RO+CD25+Foxp3+CD127lo. The frequency of circulating Tregs was quantified within the CD4+ T-lymphocyte population at the time of neutrophil engraftment. CLA+ Tregs (considered skin-homing) and α4 β7+ Tregs (considered gut-homing) were enumerated as their respective subpopulations within the total Treg population. Results:New-onset PTDM occurred in 24 (66.7%) patients at a median of 24.5 days post-HCT (range, 7–100 days). PTDM was diagnosed prior to grade II-IV acute graft-versus-host disease (GVHD) (N= 28) or the start of systemic corticosteroids (N= 28) in 12 (50%) and 14 (58%) patients, respectively. Clinical characteristics, including acute GVHD or treatment with corticosteroids, were not associated with the development of PTDM. Median follow-up was 2.9 years (range, 0.5–4.0 years) for surviving patients (N= 22). Overall survival and non-relapse mortality at 2 years was 45.8% and 29.2% among patients with PTDM and 100% and 0% for those without diabetes (P= 0.052, P= 0.017). PTDM was not associated with relapse. Treg analysis was performed at a median of 19 days (range, 12–27 days) post-HCT and prior to the diagnosis of PTDM in 9 (37.5%) patients. The percentage of circulating CLA+ Tregs at engraftment was significantly lower in patients with PTDM (median, 1.53% vs. 3.99%; P= 0.002). Conversely, PTDM was associated with increased frequencies of α4 β7+ Tregs [median, 17.9% vs. 10.7%; P= 0.048 (PTDM vs. no PTDM)]. The skewing of the Treg phenotype was demonstrated further by the ratio of α4 β7+ Tregs to CLA+ Tregs, which was significantly higher in patients with PTDM (median, 8.93% vs. 1.85%; P= 0.004). The cumulative incidence of day+100 PTDM was 75.0% in individuals with ratios of α4 β7+ Tregs to CLA+ Tregs greater than or equal to the cohort median of 6.32, compared with 44.4% in those with a ratio less than the median (P= 0.005). The analyses were repeated using only patients who had grade II-IV acute GVHD treated with systemic corticosteroids (N= 26). Similar results were found, with decreased CLA+ Tregs (P= 0.013) and increased α4 β7+ Tregs (P= 0.048) among HCT recipients with PTDM. There was no significant association between PTDM and the percentage of CD4+ memory T cells, CD4+CLA+ T cells, CD4+ α4 β7+ T cells, or total Tregs (not accounting for homing properties). Using logistic regression (adjusted for conditioning, donor type, and corticosteroids), patients with PTDM continued to demonstrate an elevated ratio of α4 β7+ Tregs to CLA+ Tregs (odds ratio, 10.6; 95%CI, 1.55–71.9; P= 0.016). Conclusion:The distribution of Tregs with specific tissue-homing properties was markedly altered in patients who developed PTDM. These data suggest that PTDM and insulin resistance are associated with cellular immune responses post-HCT including Treg subset frequencies and immune regulation. PTDM and the related metabolic syndrome could represent an important new therapeutic target to modulate alloreactivity and clinical outcomes following HCT. Disclosures:No relevant conflicts of interest to declare.

Nilotinib Exerts Direct Effects on Vascular Endothelial Cells and May Act As a Co-Trigger of Atherosclerosis in Patients with Ph+ CML

Abstract▪2753▪This icon denotes a clinically relevant abstractThe second-generation BCR/ABL tyrosine kinase inhibitor nilotinib is increasingly used for the treatment of patients (pts) with newly diagnosed Ph+ CML or imatinib-resistant CML. So far, nilotinib has been considered a well-tolerated drug that shows little if any relevant side effects. However, long-term results are not available yet. Known recurrent side effect of nilotinib include an increase in pancreatic enzymes (lipase, amylase) and an increase in fasting glucose levels. More recently, several centers have reported on the occurrence of progressive peripheral arterial occlusive disease (PAOD) in some of their pts treated with nilotinib. The exact relationship with drug intake and the potential mechanisms underlying PAOD development remain unknown. To address these questions, we have extended and updated our retrospective analysis and examined the in vitro effects of nilotinib. A total number of 34 pts (second line nilotinib, n=33; first line nilotinib, n=1; females, n=15; males, n=19, median age: 57.5 years) receiving nilotinib in our center were examined (observation period 2006–2011). Vascular events related to atherosclerosis were recorded in 9 pts (26.5%). Of these, 6 (17.6%) had PAOD, including 2 cases of severe PAOD requiring repeated surgical interventions or amputation (n=1). One patient had a myocardial infarction, one an acute coronary artery syndrome requiring bypass surgery, and one a spinal infarction. Although in all 9 pts, one or more pre-existing risk factors for atherosclerosis were identified, none of these pts had developed a vascular event during prior imatinib therapy. The JAK2 V617F mutant was not found in any of the 9 pts. Three pts died during the observation period, two from major bleeding episodes, and one from sudden death of unknown etiology. In 5 cases, an increase in blood glucose levels was found, and 1 patient developed overt diabetes mellitus. The frequency of PAOD development in age-, observation time-, and risk factor-matched control cohorts (CML pts receiving imatinib, lymphoproliferative neoplasms, JAK2 V617F+ myeloproliferative neoplasms, each n=34 pts) was significantly lower (<5%) than in the nilotinib group (p<0.05 by Chi Square test with Boneferroni correction). As assessed by 3H-thymidine uptake, nilotinib was found to inhibit the growth of the human microvascular endothelial cell line HMEC-1 (IC50: 0.5–1.5 μM), whereas no substantial effect was seen with imatinib. Furthermore, nilotinib, but not imatinib, was found to inhibit umbilical vein endothelial cell (HUVEC) migration and sprouting in a scratch-wound healing assay. Finally, nilotinib but not imatinib, was found to block the growth of various human pancreatic cell lines, including PANC-1 and the insulin- producing cell line 1.4E7. Together, our data show that nilotinib exerts direct inhibitory effects on endothelial cells and pancreatic cells. Whether these drug effects contribute to vascular events seen in our nilotinib-treated pts remains at present unknown. In addition, the exact pro-atherogenic effect of nilotinib in second-line and first-line treated patients with CML remains unknown since no data from prospective clinical trials focusing on this issue, are available. Until these questions and safety-issues have been clarified, it may be advisable to take certain co-morbidities into account when considering the use of nilotinib in CML patients. In addition, the follow up of long-term treated patients should include parameters that can detect vascular events and predisposing co-morbidities as early as possible. Disclosures:Valent:Novartis: Consultancy, Honoraria, Research Funding.

Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus)

BackgroundThe PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease.MethodsPANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors.ResultsThe mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001).ConclusionsAsymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered.Trial registration numberClinicalTrials.gov: NCT00689377

Serum adiponectin level is not only decreased in metabolic syndrome but also in borderline metabolic abnormalities

Objective:Along with the increasing prevalence of obesity and related diseases, particularly atherosclerotic diseases, metabolic syndrome (MetS) is now a common and major public health issue in many countries around the world. Adiponectin, a protein secreted by the adipose tissue, has become recognized as a key player in the development of MetS. These days, not only MetS but also borderline metabolic/physiological abnormalities, such as impaired fasting glucose, high normal blood pressure and high normal plasma cholesterol, have been reported to be risk factors for atherosclerotic disease. Therefore, we undertook this study to determine the relationship between adiponectin and borderline metabolic/physiological abnormalities, as well as MetS.Design:A cross-sectional study performed from April 2007 to November 2009.Subjects:In 16 892 Japanese adults (10 008 men and 6884 women), we examined the relationship between the serum adiponectin concentration and borderline metabolic/physiological abnormalities or MetS by a questionnaire survey about medical treatment, body size measurement and measurement of laboratory parameters including the serum adiponectin concentration.Results:Adiponectin showed a significant negative correlation with the number of MetS components. In subjects without overt diabetes mellitus, hypertension or dyslipidemia, the adiponectin concentration also showed a significant negative correlation with the number of borderline metabolic abnormalities.Conclusion:The decrease of circulating adiponectin may start before the development of diabetes mellitus, hypertension, dyslipidemia or MetS. Adiponectin is an important biomarker for reflecting the adverse influence of visceral fat in persons with MetS, and also in these subclinical states.

Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of characteristic co-morbidities that interfere with their pulmonary disease. In addition to a mere association with co-morbidities, a complex pathophysiological interaction and mutual augmentation occurs between COPD and its co-morbidities that may result in disease progression and increased morbidity and mortality. An interdisciplinary approach is required both for diagnosis and treatment to target co-morbidities early in the course of the disease. This review summarizes the current knowledge of the interaction with cerebrovascular disease and endocrinological co-morbidities in COPD patients. There is growing evidence that COPD is an independent risk factor for ischemic stroke, increasing the risk about twofold. Stroke risk in COPD patients increases with the severity of the disease as measured by the degree of airflow limitation. The presence of cardiovascular risk factors is of particular importance for stroke prevention in COPD patients. Endocrinological co-morbidities are also important and many are associated with increased cardiovascular risk. Impaired glucose metabolism ranges from insulin resistance to overt diabetes mellitus, which is a frequent finding and is associated with worse outcome.

Therapeutic approach for type 1 diabetes mellitus using the novel immunomodulator FTY720 (fingolimod) in combination with once-daily injection of insulin glargine in non-obese diabetic mice.

Aims/Introduction: The therapeutic effectiveness against type 1 diabetes mellitus (DM) of the novel immunomodulator FTY720 (fingolimod), alone and in combination with insulin glargine, was examined in the non-obese diabetic (NOD) mouse model. Female NOD mice that had developed DM spontaneously were divided into four groups: (i) an FTY720 (0.1 mg/kg, p.o., twice weekly)-treated group; (ii) an insulin glargine (1.0 IU, s.c., once daily)-treated group; (iii) a combination FTY720 + insulin glargine (0.1-1.0 IU, s.c., once daily)-treated group; and (iv) a placebo (vehicle)-treated group. Treatment was initiated at the time of onset of DM and continued for 70 days or until death. The therapeutic efficacy of FTY720, insulin glargine and FTY720 + insulin glargine was evaluated by measuring the ratio of insulin-positive β-cells/total islet area, the extent of islet inflammation (insulitis score), blood glucose levels, and serum C-peptide levels. Therapeutic administration of FTY720 to NOD mice with hyperglycemia (i.e. overt DM) significantly prolonged survival (P < 0.05 vs placebo). In the placebo group, all mice died within 63 days on the onset of DM; in contrast, 45% of FTY720-treated mice survived during the observation period (up to 70 days after the onset of DM). Therapeutic administration of FTY720 in combination with insulin glargine to NOD mice with hyperglycemia further improved survival (P < 0.05) compared with either FTY720 or insulin glargine alone (i.e. 85% of FTY720 + insulin glargine-treated mice survived to the end of the observation period). The efficacy of FTY720 in combination with insulin glargine was confirmed by histochemical, immunohistochemical and endocrinologic observations. Combination therapy with FTY720 plus insulin glargine is a promising candidate for the treatment of DM and may allow for a reduction in the frequency of insulin self-injections. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00160.x, 2011).

Histopathological placental lesions in mild gestational hyperglycemic and diabetic women.

ObjectiveTo investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation.Research design and methodsOne-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM) positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT) in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH), gestational DM (GDM) or overt DM (DM). Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin.ResultsPlacentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon.ConclusionOur results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

Insulin therapy in patients with cystic fibrosis related diabetes mellitus: benefit, timing of initiation and hypoglycaemia

AbstractPancreatic endocrine dysfunction in patients with cystic fibrosis heralds declining pulmonary function and a six‐fold rise in mortality. Insulin therapy increases weight and reduces decline in lung function. Optimal timing of initiation remains contentious but early intervention may maximise benefit. We explored the optimal timing of initiation of therapy and characterised the frequency and usual symptoms of hypoglycaemia.Fifty‐four patients with cystic fibrosis treated with insulin were compared up to five years pre and post insulin initiation with respect to weight gain and lung function. Frequency and usual symptoms of hypoglycaemia were assessed using the Hypoglycemia Symptoms Awareness Questionnaire.Mean age was 27.6(16–52) years. In the five years preceding insulin therapy, FEV1 declined from 2.6±0.14L to 1.78±0.12L (p&lt;0.001). In the group as a whole, rate of decline was arrested with insulin initiation; the mean five‐year post insulin FEV1 was 1.74±0.20L (p=0.15). When stratified according to oral glucose tolerance testing at initiation the rate of decline was significant in patients with impaired glucose tolerance (p=0.02) but not normal glucose tolerance nor overt cystic fibrosis diabetes mellitus. Insulin therapy increased weight from 53.08±1.53kg to 56.22±2.08kg (p=0.05). Hypoglycaemia was common and 75% of respondents scored results indicative of hypoglycaemia unawareness.This study confirms that the favourable effect of insulin upon lung function in patients with cystic fibrosis correlates with the degree of glucose intolerance at baseline. Hypoglycaemia is an important clinical issue. Copyright © 2011 John Wiley &amp; Sons.

High prevalence of abnormal glucose regulation in patients presenting for routine coronary angiography

AbstractAbnormal glucose metabolism is a known risk factor for coronary artery disease (CAD) and is frequently unrecognised even in patients with acute coronary syndrome. Patients with stable coronary symptoms frequently have multiple risk factors and may have no assessment of glucose regulation. The purpose of this study was to assess the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) in a group of patients with stable symptoms presenting for coronary angiography. A modified oral glucose tolerance test (OGTT) was performed on 182 unselected patients undergoing elective angiography. Patients with known DM were excluded. Demographic data including cardiovascular risk factors, body mass index (BMI), and history of CAD were recorded. In all, 182 patients with a mean age of 62.1 years (±10.7 years) were studied. Indications for angiography were suspected angina. By WHO criteria an abnormal two‐hour glucose was present in 49% of individuals, with 10.4% of these patients having overt DM. An abnormal two‐hour glucose was seen in 63.2% of patients with significant CAD compared with 40.3% with normal or insignificant disease (p=0.004); 48.9% of patients with IGT or DM had normal fasting plasma glucose (FPG). In 78% of patients, BMI was over 25kg/m2. In this high risk population with multiple risk factors for CAD, previously undetected IGT and overt DM are very common. Almost two‐thirds of patients with significant CAD had abnormal glucose regulation. The use of an FPG test alone may miss a significant number of patients with unrecognised glucose intolerance. Copyright © 2011 John Wiley &amp; Sons.

Primiparity at Very Advanced Maternal Age (≥45 years)

This study describes maternal and birth outcomes of primiparae aged ≥ 45. High rates of pregnancy complications and poor birth outcomes were found, stressing that the personal risks and ramifications to the health system should be taken into account in establishing obstetric health policy regarding primiparity at advanced maternal age.

Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus

Objectives:An impaired heart rate response during exercise (chronotropic incompetence) and an impaired heart rate recovery (HRR) after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.Method:Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.Results:The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 μg/L; P < 0.001). The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 μg/L; P = 0.005). Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186). Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259). HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2 ± 4.5 per min; P < 0.001), and the ST-segment adjustment relative to heart rate(ST/HR index ratio) was 1.4 ± 1.34 versus 0.4 ± 0.31 μV/beat (P < 0.001), respectively. Cystatin C was negatively correlated with the chronotropic response index (CRI) and HRR and was positively correlated with ST/HR index in the entire study population (R = −0.658, −0.346, 0.388, respectively; P < 0.05).Conclusions:A substantial proportion of metabolic syndrome patients without overt diabetes mellitus had silent coronary ischemia in addition to impairment of objective exercise electrocardiographic parameters. In the metabolic syndrome patients without overt diabetes mellitus, cystatin C levels were found to be elevated and the elevation was more pronounced in the subgroup with silent ischemia. Cystatin C was also correlated with HRR and CRI.

Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics

We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery. Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by ¹H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by "targeted profiling" followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308). The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions. Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry.

The impact of transsphenoidal surgery on glucose homeostasis and insulin resistance in acromegaly

Background and purposeImpaired glucose tolerance and overt diabetes mellitus are frequently associated with acromegaly. The aim of this study was to find out whether these alterations could be reversed after transsphenoidal surgery. Material and methodsTwo hundred and thirty-nine acromegalic patients were studied before and 6–12 months after transsphenoidal surgery. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In each patient, glucose and insulin concentrations were assessed during the 75 g oral glucose tolerance test (OGTT). To estimate insulin resistance, we used homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). ResultsAt the moment of diagnosis, diabetes mellitus was present in 25% of the acromegalic patients. After surgery, the prevalence of diabetes mellitus normalized to the level present in the general Polish population. We found a statistically significant reduction after surgery in plasma glucose levels both fasting (89.45 ± 13.92 mg/dL vs. 99.12 ± 17.33 mg/dL, p < 0.001) and during OGTT. Similarly, a prominent reduction in insulin secretion was found after surgery compared to the moment of diagnosis (15.44 ± 8.80 mIU/mL vs. 23.40 ± 10.24 mIU/mL, p < 0.001). After transsphenoidal surgery, there was a significant reduction in HOMA-IR (3.08 vs. 6.76, p < 0.0001) and a significant increase in QUICKI (0.32 vs. 0.29, p < 0.001). There were no statistically significant differences after surgery in fasting glucose and insulin levels between patients with controlled and inadequately controlled disease. ConclusionsWe conclude that in acromegalic patients glucose homeostasis alterations and insulin sensitivity can be normalized after transsphenoidal surgery, even if strict biochemical cure criteria are not fulfilled.

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.