Recent-onset Diabetes Mellitus Research Articles

The association between diabetes mellitus of different durations and risk of pancreatic cancer: an Australian national data-linkage study in women

AimsThe bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation. MethodsWe conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity. ResultsThe analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96–2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88–9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27–1.55). ConclusionThe markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.

Is ectopic Cushing's syndrome underdiagnosed in patients with small cell lung cancer?

IntroductionEctopic Cushing’s syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing’s syndrome (CS) had ECS than has previously been reported.ObjectiveThe aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC).Materials and methodsMedical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36–89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia.ResultsOf 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively).ConclusionsOur findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.

Emergence of Invasive Fungal Rhinosinusitis in Recently Recovered COVID-19 Patients.

The risk of invasive fungal rhinosinusitis is increased in Coronavirus disease 2019 (COVID-19) because of its direct impact in altering innate immunity and is further exacerbated by widespread use of steroids/antibiotics/monoclonal antibodies. The study aims to describe this recently increased clinical entity in association with COVID-19. A prospective, longitudinal study including patients diagnosed with acute invasive fungal rhinosinusitis (AIFRS) who recently recovered from COVID-19 infection or after an asymptomatic carrier state. A single-center, descriptive study investigating demographic details, clinical presentation, radio-pathological aspects, and advocated management. A total of 21 patients were included with a mean age of 49.62 years (SD: 14.24). Diabetes mellitus (DM) was the most common underlying disorder (90.48%), and 63.16% of all patients with DM had a recent onset DM, either diagnosed during or after COVID-19 infection. Nineteen patients (90.48%) had recently recovered from active COVID-19 infection, and all had a history of prior steroid treatment (oral/parenteral). Remaining 2 patients were asymptomatic COVID-19 carriers. Surprisingly, 2 patients had no underlying disorder, and 5 (23.81%) recently received the Covishield vaccine. Fungal analysis exhibited Mucor (95.24%) and Aspergillus species (14.29%). Most common sign/symptom was headache and facial/periorbital pain (85.71%), followed by facial/periorbital swelling (61.90%). Disease involvement: sinonasal (100%), orbital (47.62%), pterygopalatine fossa (28.58%), infratemporal fossa (14.29%), intracranial (23.81%), and skin (9.52%). Exclusive endoscopic debridement and combined approach were utilized in 61.90% and 38.10%, respectively. Both liposomal amphotericin B and posaconazole were given in all patients except one. A high suspicion of AIFRS should be kept in patients with recent COVID-19 infection who received steroids and presenting with headache, facial pain, and/or facial swelling. Asymptomatic COVID-19 carriers and COVID-19 vaccinated candidates are also observed to develop AIFRS, although the exact immuno-pathogenesis is still unknown. Prompt diagnosis and early management are vital for a favorable outcome.

Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients

ABSTRACT Purpose To report a series of 13 immunocompetent patients who developed new-onset uncontrolled diabetes mellitus (DM) following COVID-19 infection and presented as rhino-orbital mucormycosis (ROM). Method Retrospective study. Results A total of 127 patients of COVID-19 Associated Mucormycosis (CAM) were evaluated at four centres in India. All patients underwent endoscopic sinus debridement surgery and received systemic amphotericin-B therapy. Five patients (5/13; 38.4%) received retrobulbar amphotericin-B injections. Orbital exenteration was performed in advanced orbital involvement or progression of orbital disease in spite of maximal medical therapy. In his cohort, 13/127 (10.2%) patients presented with new onset DM, where one patient had bilateral disease. The mean age was 35.9 years (range: 20–51 years) and the mean duration from diagnosis of COVID-19 to the diagnosis of mucormycosis was 14.2 days. While 7/13 (53.8%) of the patients received systemic corticosteroids during the course of their treatment for COVID-19, six patients received no steroids or immunomodulators. The mean follow-up period was 9.2 weeks (range: 3–18 weeks) following discharge. Life salvage was possible in 100% of the cases. While overall globe salvage was possible in 42.8% (6/14 eyes), the globe could be preserved in 4/5 patients who received retrobulbar amphotericin-B injections. Conclusions Those involved in the care of COVID-19 patients should be aware about the possibility of recent-onset DM, even in patients without a history of corticosteroid therapy. Rarely, recent-onset DM following COVID-19 may present as rhino-orbital mucormycosis, which requires aggressive surgical and medical intervention.

Early Detection of Pancreatic Cancer in Type 2 Diabetes Mellitus Patients Based on 1H NMR Metabolomics.

The association of pancreatic cancer with type 2 diabetes mellitus was investigated by 1H NMR metabolomic analysis of blood plasma. Concentration data of 58 metabolites enabled discrimination of pancreatic cancer (PC) patients from healthy controls (HC) and long-term type 2 diabetes mellitus (T2DM) patients. A panel of eight metabolites was proposed and successfully tested for group discrimination. Furthermore, a prediction model for the identification of at-risk individuals for future development of pancreatic cancer was built and tested on recent-onset diabetes mellitus (RODM) patients. Six of 59 RODM samples were assessed as PC with an accuracy of more than 80%. The health condition of these individuals was re-examined, and in four cases, a correlation to the prediction was found. The current health condition can be retrospectively attributed to misdiagnosed pancreatogenic diabetes or to early-stage pancreatic cancer.

Diabetes mellitus in intraductal papillary mucinous neoplasm of the pancreas is associated with high-grade dysplasia and invasive carcinoma

BackgroundWhile the association between Diabetes Mellitus (DM) and pancreatic ductal adenocarcinoma is well recognized, its importance in intraductal papillary mucinous neoplasm of the pancreas (IPMN) is not well-defined. We sought to examine the associations of DM with degree of dysplasia and morphological subtypes in IPMN. MethodsIn 454 patients with resected IPMN, we evaluated associations of DM with high-grade dysplasia (HGD), invasive carcinoma, precursor epithelial subtype (gastric, intestinal, oncocytic, pancreatobiliary), and histological type of invasive carcinomas (tubular, colloid, oncocytic) using logistic regression. We performed multivariate analyses adjusting for worrisome features and high-risk stigmata of malignancy in a subset of 289 patients with annotated radiological characteristics. ResultsThe prevalence of DM in our study was 34%. DM was significantly associated with HGD (OR 2.02, 95% CI 1.02–4.01, P = 0.045) and invasive carcinoma (OR 2.05, 95% CI 1.08–3.87, P = 0.027) after adjusting for worrisome features. Compared to patients without DM, those with recent-onset DM (≤5 years before surgery) had 6.9-fold (95% CI 2.38–19.92, P < 0.001) higher risk of invasive carcinoma. DM was associated with increased likelihood of intestinal-type precursor epithelium (OR 1.63, 95% CI 1.07–2.47, P = 0.022) and colloid carcinomas (OR 2.46, 95% CI 1.01–5.99, P = 0.047) ConclusionPreoperative DM was associated with significantly higher risk of HGD and invasive carcinoma in resected IPMN, and risk of invasive carcinoma was highest in patients with recent-onset DM. Patients with DM were more likely to harbor intestinal-type IPMN and colloid carcinomas. Our findings suggest that a diagnosis of DM in patients with IPMN may warrant more aggressive surveillance.

Etiopathological differentiation of diabetes mellitus in lean, young adults

ObjectiveClassification of diabetes mellitus (DM) into type 1 or type 2 is difficult in lean, young individuals. We studied the β-cell function, insulin resistance (IR) and autoimmunity in young patients with recent onset DM. MethodsIn this cross-sectional study, we included patients (age below 35 years) with recent onset DM (<6 months) and normal body weight for evaluation. The detailed clinical examination was done to identify markers of IR. Autoimmune DM was diagnosed using glutamic acid decarboxylase 65 (GAD65), insulin autoantibody (IAA) and islet cell antibody (ICA). Homeostasis model assessment (HOMA) models of HOMA-B and HOMA- IR were used for estimation of β-cell function and IR respectively. The patients were divided into four groups based on, the autoimmunity (A) and ketosis (K) as group 1 (A+K), group 2 (A−K+), group 3 (A+K−) and group 4 (A−K−). Appropriate statistical tests +)were used to analyze the results. ResultsThe study population (n=75, all males) had a mean age of 28.9±4.3years, body mass index 20.6±1.9kg/m2, fasting plasma glucose 177.1±31.4mg/dl and HbA1c of 9.9±2.1% at presentation. The number of patients in groups 1 to 4 are 8, 5, 10 and 52 respectively (p<0.0001). HOMA-IR was higher in groups 2 and 4 (4.1±1.3, 3.6±1.1 respectively), whereas HOMA-B was higher in group 4 (3.6±1.5) alone (p=0.0005). ConclusionType 2 DM is the most common etiology even in young, lean adults in India. Further studies with large numbers are required to confirm our findings.

Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study.

AimTo investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC)MethodsProspective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery).ResultsOf 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06–1.99]).ConclusionPreoperative recent onset DM has an impact on survival after the resection of PDAC.

Genetic causes of maturity onset diabetes of the young may be less prevalent in American pregnant women recently diagnosed with diabetes mellitus than in previously studied European populations

Context: There are many causes of impaired glucose tolerance in pregnant women. It is unclear whether genetic etiologies are a source of impaired glucose tolerance in pregnant women.Objective: To prospectively determine the prevalence of maturity onset diabetes of the young (MODY) due to glucokinase (GCK) mutations in an American population of women with recent onset diabetes mellitus and gestational diabetes. We hypothesized that based on America’s higher prevalence of gestational diabetes mellitus (GDM) and Type 2 diabetes, there may be an increased prevalence of GK mutations in our population than in previously reported studies from European studies.Design: Over a three-year period, 72 pregnant women with recently diagnosed diabetes mellitus were prospectively assessed for presence of the most common pathogenic GCK mutations.Setting: This study was performed in a gestational diabetes clinic in Urban America and a high-risk pregnancy clinic that served the military and their families on an American military base in Germany.Patients: Seventy-two women; 65 with diagnosis of diabetes mellitus in this pregnancy (GDM/overt diabetes) and 7 with diagnosis in the last nine years prior to pregnancy were recruited during pregnancy and blood samples were obtained.Interventions: None.Main outcome measures: Each study participant’s blood sample was analyzed with restriction fragment length polymorphism to assess for mutations in the GCK gene.Results: There were 38 female and 34 male neonates born at 38 weeks gestation ±1.2 weeks. Mean birth weight was 3351 g ± 450 g. There were no patients with GCK mutations found in our population 0/72. This prevalence is not greater than that seen in previous a similar study in European women with gestational diabetes, but in fact significantly less (p = 0.03).Conclusion: American women with recently diagnosed diabetes mellitus likely have no higher prevalence of MODY than in previously studied European women with diabetes mellitus and may have a lower prevalence.

The impact of diabetes mellitus and metformin on survival of patients with advanced pancreatic cancer receiving chemotherapy.

4044 Background: A causal relationship between diabetes mellitus (DM) and pancreatic cancer (PC) is well established. However, in patients with advanced PC (APC) who receive palliative chemotherapy, the impact of DM on prognosis is unclear. Methods: Between 2003 and 2010, we enrolled consecutive patients with APC, all recipients of palliative chemotherapy, with the provision that DM disease status could be properly defined. Enrollees were stratified by diagnosis, in accordance with 2010 DM criteria (AHA/ADA). DM at least 2 years' duration prior to diagnosis of APC qualified as remote-onset DM (vs recent-onset). Clinical characteristics and outcomes were then analyzed. Results: Of the 349 enrollees with APC, 183 (52.4%) had DM. In patients with DM, 160 had DM at the time APC was diagnosed (remote onset, 87; recent onset, 73); and the remaining 23 developed DM during the course of APC treatment. Ultimately, 73.2% (134/183) of DM patients received antidiabetic medication (metformin (56), sulfonylurea (62), insulin (43)). By multivariate analysis, cancer extent (HR, 1.792; p &lt; 0.001) and weight loss during chemotherapy (HR, 1.270; p = 0.08) were associated with diminished overall survival (OS), whereas a diagnosis of DM (HR, 0.788; p = 0.05) conferred a positive effect on OS ( OS 8.4 months in DM patients vs 7.5 months in non-DM patients, p = 0.04). Among DM patients, recent-onset DM trended toward prolonged OS, compared with remote-onset/subsequent DM (9.8 months vs. 7.9 months, respectively; HR, 0.789; p = 0.142). Neither antidiabetic medication in general nor sulfonylurea or insulin specifically affected OS. However, recipients of metformin survived longer than non-recipients (HR, 0.693; 95% CI, 0.492-0.977; p = 0.036). Relative to the APC cohort overall including non-DM patients, metformin conferred better survival as well (11.0 months vs. 7.8 months, HR 0.712, p = 0.067), given similar baseline clinical characteristics. Conclusions: In patients with APC receiving palliative chemotherapy, recent-onset DM (within 2 years of APC diagnosis) and metformin treatment are positive prognosticators, associated with prolonged OS.

Intraoperative pancreatoscopy with narrow band imaging: a novel method for assessment of resection margins in case of intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is characterized by intraductal proliferation of neoplastic mucinous cells with a variable extent along the main duct or its branches. The lesion may be continuous or discontinuous. Skip lesions have been described in about 6-19% of cases. Complete resection without leaving behind any skip lesions is important, to such an extent that many groups suggest even total pancreatectomy, a major and morbid surgery. A 40 year-male patient with chronic pancreatitis presented with recent-onset diabetes mellitus and weight loss. Ultrasound and computed tomography (CT) scan showed a cystic lesion in the head and uncinate process of pancreas. Peroral pancreatoscopy showed villous projections with dilated tortuous vessel in the head, suspicious of IPMN. The duct beyond pancreatic head could not be visualized and remained unassessed. At pancreatoduodenectomy, pancreatoscopy with narrow band imaging (NBI) was done using flexible pancreatoscope through the cut end of the duct at the neck to assess the duct in the body and tail. Pancreatoscopy with NBI showed a normal-looking resection margin and a skip lesion 1 cm beyond it. The revised resection margin confirmed the skip lesion on frozen section and also that the fresh cut margin was negative. The remaining duct in the body and tail was normal on pancreatoscopy. Total clearance of the disease could be achieved without a major procedure such as total pancreatectomy. Intraoperative pancreatoscopy, especially with NBI, is a good diagnostic tool for IPMN and also helps in intraoperative decision-making of the resection margins.

Modulatory effect of insulin on T cell receptor mediated calcium signaling is blunted in long lasting type 1 diabetes mellitus

AbstractInsulin significantly influences Ca2+ signals evoked by various stimulants. In type 1 recent onset diabetes mellitus the proliferative response of T cells is significantly decreased. The number of clinical trials exploring the role of anti-CD3 monoclonal antibodies (mAb) as a therapeutic agent in recent onset diabetes mellitus type 1 is increasing last years. Therefore, a better understanding of the interplay between T cell receptor (TCR) dependent Ca2+ increase, and insulin is of vital clinical significance. The aim of the study was to assess the effect of insulin on TCR evoked Ca2+ responses in T lymphocytes obtained from healthy volunteers and patients suffering from long lasting diabetes mellitus type 1. Analysis was performed with use of the flow cytometer. We demonstrated that T cells ability to mobilize Ca2+ was significantly reduced in long lasting diabetes mellitus type 1. Ca2+ decrease achieved by the long term incubation with anti-CD3 mAb in T cells from healthy volunteers was restored by insulin. Strong interrelationship between baseline Ca2+ level and plateau phase response to TCR stimulation was observed in the cytoplasm of cells pre-incubated with insulin from both healthy subjects and diabetic patients (r=0.95, p<0.0001 and r=0.94, p<0.0001, respectively). We postulate the existence of the interplay between TCR mediated activation and insulin. The TCR-insulin interplay is blunted in long lasting diabetes mellitus type 1. These observations may have an important implication for future therapeutic options in diabetes.

Cardiovascular disease in recent onset diabetes mellitus

Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in the diabetic population. Furthermore, recently, macrovascular complications of diabetes have been shown to start before the onset of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since insulin resistance-related postprandial metabolic derangements are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial metabolic disturbance is a therapeutic target for the prevention of CVD in these high-risk patients. Therefore, in this paper, we review the molecular mechanisms for the increased risk of CVD in recent onset diabetes mellitus, especially focusing on postprandial dysmetabolism. We also discuss here the potential therapeutic strategies that specially target the mechanisms responsible for vascular alterations in diabetes.

Severe hypercortisolism: A medical emergency requiring urgent intervention

To illustrate the importance of recognizing symptoms of severe hypercortisolism in the intensive care unit and key emergency measures to reduce this extreme hypercortisolism. Case report. Intensive care unit in a university hospital. A 55-yr-old woman was admitted to the intensive care unit with multiorgan failure after perforation of the sigmoid. Recent-onset hypertension, spontaneous hypokalemia, and diabetes mellitus suggested severe Cushing's syndrome as the underlying disease. Markedly increased serum cortisol (5900 nmol/L) and adrenocorticotropic hormone (302 ng/L) levels were found, highly suggestive for ectopic adrenocorticotropic hormone secretion. Imaging studies failed to unequivocally establish a solitary source of ectopic adrenocorticotropic hormone secretion. The deteriorating condition of the patient urged rapid intervention. Etomidate was infused continuously to reduce endogenous adrenal cortisol secretion. Subsequently, a rescue bilateral adrenalectomy was undertaken. Etomidate effectively reduced the cortisol level. Serial blood samples were obtained during the bilateral adrenalectomy. Plasma adrenocorticotropic hormone markedly decreased immediately after resection of the right adrenal gland. Histopathological examination revealed a tumor of the right adrenal gland identified as a pheochromocytoma and hyperplasia of the left adrenal gland, but no signs of malignancy. The patient recovered slowly. This case illustrates that severe hypercortisolism is a medical emergency and that specific and prompt combined medical and surgical intervention can be life-saving.

Is it possible to reduce cardiovascular risk with glucose-lowering approaches?

Diabetes mellitus is a strong, independent risk factor for cardiovascular events, and a key determinant of the level of this risk is the degree of glucose elevation. Clinical trials have not demonstrated that lowering glucose levels in people with established, long-duration diabetes mellitus has a clear cardiovascular benefit, and one trial reported that this approach increased mortality. In individuals with recent-onset diabetes mellitus, however, control of glucose level has established benefits on diabetes-related eye disease and kidney disease (which are themselves cardiovascular risk factors), and 10 years of intensive glucose control in these patients reduces the 15-20-year risk of myocardial infarction and mortality. These observations, along with the facts that the prevalence of diabetes mellitus is growing and that people typically have the disease for 20-40 years of their lives, support the importance of controlling glucose level and preventing its progressive rise over time. Currently available evidence suggests that therapeutic efforts that target hyperglycemia early in the course of diabetes have a long-term cardiovascular benefit.

Prevalence of Pancreatic Cancer in Diabetics and Clinical Characteristics of Diabetes-associated with Pancreatic Cancer - Comparison between Diabetes with and without Pancreatic Cancer -

In Korea, the prevalence of pancreatic cancer (PC) in general population has been reported as 7 in 100,000. However, that in diabetes mellitus (DM) has not been elucidated yet. This study was designed to estimate the prevalence of PC among DM patients, and characterize and compare the patients with DM with and without PC. 5,082 patients (4,890 DM without PC, 78 PC with DM, and 114 PC without DM) were enrolled from Korea University Guro Hospital during a period of 4 years between January 2004 and January 2008. The prevalence of PC in DM patients was 1.6% and that of DM in PC patients was 40.6%. No significant differences in the clinical characteristics except HbAIc and ALP were observed between PC patients with DM and without DM. Among 78 PC patients with DM, DM was diagnosed in 19 (29.4%) and 29 (37.1%) patients concomitantly or within 2 years prior to the diagnosis of PC, respectively. Among the cases with recent onset DM (less than 2 years duration), the disease duration of DM before the diagnosis of PC was less than 1 year in 14 patients (17.9%) and 1 to 2 years in 15 patients (19.2%). DM patients with PC were found to have significantly higher ALT, total bilirubin, and ALP levels than in DM patients without PC. The prevalence of PC in DM patients was 1.6% and was higher than in the general population. Recent onset DM was frequent in PC patients (less than 2 years duration). We recommend close follow-up for at least 2 years in new-onset diabetes.

Myocardial involvement during the early course of type 2 diabetes mellitus: usefulness of Myocardial Performance Index

To evaluate whether myocardial performance index detects a subclinical impairment of left ventricular systolic and diastolic function in patients with early stage of type 2 diabetes, without coronary artery disease, with or without hypertension. Furthermore, to evaluate whether some echocardiographic parameters relate to the metabolic control. Fourty-five consecutive male patients (mean age 52.5 years) with type 2 diabetes mellitus of recent onset (23 hypertensives and 22 normotensives) and 22 age matched healthy controls males were analysed. All participants had normal exercise ECG. All subjects underwent standard and Doppler echocardiography for the assessment of the isovolumic Doppler time interval and Doppler-derived myocardial performance index. In all diabetic patients a glycated haemoglobin test was also performed.No differences were observed in blood pressure, heart rate, and conventional echocardiographic parameters comparing the 2 subgroups of diabetic patients and the controls. Myocardial performance index was significantly higher in diabetic patients independently of the hypertension occurrence, compared to the controls (0.49 and 0.49 diabetic normotensives and hypertensives respectively vs. 0.39, p < 0.01). Myocardial performance index correlated to glycated haemoglobin significantly (r = 0.37, p < 0.01) in both diabetic subgroups. Thus, an early involvement of left ventricular performance was shown by myocardial performance index in patients with type 2 diabetes of recent onset without coronary artery disease, independently of the hypertension presence. These abnormalities can provide a feasible approach to detect a pre-clinical diabetic cardiomyopathy and could be useful for an indirect assessment of the metabolic control.

Diabetic Retinopathy: Two Faces of the Same Coin

We report two contrasting cases of diabetic retinopathy to illustrate vascular and retinal abnormalities in this condition. In the first case, mild diabetic retinopathy is diagnosed in an asymptomatic patient with diabetes mellitus of recent onset. The second patient has severe diabetic retinopathy, causing vision loss as a consequence of poor metabolic control.

Pancreatic cancer-derived S-100A8 N-terminal peptide: A diabetes cause?

Background Our aim was to identify the pancreatic cancer diabetogenic peptide. Methods Pancreatic tumor samples from patients with ( n = 15) or without ( n = 7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. Results A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C 2C 12 myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. Conclusions The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus.

Polyclonal Anti-T-Cell Therapy for Type 1 Diabetes Mellitus of Recent Onset

The destruction of pancreatic beta-cells in type 1 diabetes mellitus is mediated by autoreactive T-lymphocyte clones. We initiated a prospective randomized controlled trial of polyclonal rabbit anti-T-cell globulin (ATG) in patients with type 1 diabetes within 4 weeks of diagnosis and with residual post-glucagon C-peptide levels still over 0.3 nmol/l. ATG was administered as an initial bolus of 9 mg/kg followed by 3 consecutive doses of 3 mg/kg. An interim analysis was performed to establish whether any significant changes in C-peptide production and insulin requirement had occurred that would justify the continuation of this pilot study. By May 2004, 11 subjects were assigned to treatment with ATG along with intensified insulin therapy and 6 to intensified insulin therapy with placebo, and were followed for a period of at least 6 months. During the first 12 months a significant difference in the insulin dose trends was found between the groups (p = 0.010) with a lower insulin dosage in the ATG group. There was also a difference in the glucagon stimulated C-peptide level trends of marginal significance (p = 0.068). Compared to values at screening, stimulated C-peptide levels significantly improved in the ATG group (p = 0.012) but not in the placebo group. Complete diabetes remission occurred in 2 patients in the ATG and in none of the placebo group. Glycosylated hemoglobin at 12 months tended to be lower in the ATG group (p = 0.088). Significant adverse effects of ATG treatment, mainly transient fever and moderate symptoms of serum sickness (7 and 6 subjects, respectively) were observed during the first month only. The interim analysis of this ongoing study suggests that short-term ATG therapy in type 1 diabetes of recent onset contributes to the preservation of residual C-peptide production and to lower insulin requirements in the first year following diagnosis.