Insulin-requiring Diabetes Mellitus Research Articles

Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing's syndrome by sex: results of a multicenter study.

To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

Knowledge Regarding Hypoglycemia and Its Management Among Patients With Insulin-Requiring Diabetes Mellitus in Al-Ahsa, Saudi Arabia.

Hypoglycemia has a negative influence on patients with diabetes mellitus (DM) using insulin, and a lack of knowledge about hypoglycemia is one of the main causes of hypoglycemia. We aim to assess the level of knowledge about hypoglycemia and its management among insulin-requiring DM patients in Al-Ahsa, Saudi Arabia. A cross-sectional study was conducted on patients with insulin-requiring DM in Al-Ahsa, Saudi Arabia, from November 2021 to March 2022. A questionnaire was filled out by the participants to assess their level of knowledge about hypoglycemia, which was categorized as good, fair, or poor if participants scored >7, 6-7, or <6, respectively. A total of 238 participants were recruited. Among participants, 55% were males, mainly in the age group of 40-65 years, and had higher education degrees. Doctors were the main source of information among participants. Most patients had no chronic illnesses other than DM or DM-related complications, although hypertension was reported in 37% of patients. The majority of participants had a good level of knowledge regarding hypoglycemia, and the main factors that increased it were getting information from doctors, social media, or a booklet or pamphlet (p-value <0.05). Our participants generally had a good level of knowledge about hypoglycemia, and doctors delivering information about hypoglycemia contributed significantly to this knowledge level.

Oral anticoagulation across diabetic subtypes in patients with newly diagnosed atrial fibrillation: A report from the GARFIELD-AF registry.

This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status. The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non-DM, enrolled in the GARFIELD-AF registry. Follow-up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models. Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all-cause mortality [hazard ratio 0.75 (0.69-0.83), 0.74 (0.64-0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58-0.83), 0.70 (0.53-0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14-1.71), 1.37 (0.99-1.89), respectively]. Patients with insulin-requiring DM had a higher risk of all-cause mortality and stroke/SE [1.91 (1.63-2.24)], [1.57 (1.06-2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all-cause mortality and stroke/SE with OAC [0.73 (0.53-0.99); 0.50 (0.26-0.97), respectively]. In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all-cause mortality and stroke/SE. Patients with insulin-requiring DM derived significant benefit from OAC.

Predictors of Major Adverse Limb Events After Infrainguinal Bypass in Patients with Diabetes

ObjectiveDiabetes mellitus is a major risk factor for peripheral artery disease (PAD). The association of diabetes with major adverse limb events (MALE) after lower extremity revascularization (LER) remains controversial as patients with diabetes are often analyzed as a homogenous group. This study examines the impact of insulin use and glucose control on the outcomes of infrainguinal bypass. Our hypothesis is that insulin therapy and hemoglobin A1c (A1c) are predictors of MALE and might be used to stratify outcomes in of LER in patients with diabetes. MethodsThe Vascular Quality Initiative (VQI) database for infrainguinal bypass (2007-2021) was reviewed. Patients with diabetes undergoing bypass for PAD were included. Patients on dialysis or with kidney transplant were excluded. The characteristics and outcomes of patients with insulin requiring diabetes mellitus (IRDM) were compared with patients not requiring insulin (NIRDM). ResultsA total of 9,686 patients with diabetes (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM and more likely to be female, African American, and Hispanic. After a mean follow-up of 427 days post-operation, patients with IRDM had significantly lower primary patency and higher major amputation, MALE, and mortality. (Table) Regression analyses demonstrated that insulin use, but not A1c, was independently associated with higher risk of MALE (HR = 1.17 [1.06-1.29]) and mortality (HR=1.28 [1.16-1.43]). ConclusionPrevalent insulin use, but not the degree of A1c control, is a significant predictor of MALE and survival after infrainguinal bypass and should be used to stratify the outcomes of LER in patients with diabetes.

ODP214 INSULIN REQUIRING DIABETES MELLITUS(IRDM) and CAD

Abstract Background Several studies have shown a higher risk of coronary artery disease(CAD) in insulin-requiring T2 diabetes mellitus(IRDM) patients which could be linked with DNA methylation(proinflammatory cytokines),histone deacetylase activity(mitochondrial function-oxidant stress) and micro RNAs impacting insulin secretion and action, endothelial function and atherosclerotic process. [1,2,3,4,5]. Insulin therapy has been shown to be associated with atherosclerosis. [3]Clinical Study: A retrospective study of twenty T2 DM patients was done to observe the association of IRDM and CAD. There was equal sex distribution with mean age of 55 years in males and 50 years in females. Ten (50%)patients were insulin requiring(IRDM),having a mean insulin requirement of 0.57 units/kg in males and 0.98 units/kg in females. Seven(35%) patients had CAD;five(50%)of IRDM and two(20%)of non-insulin requiring patients. The mean insulin dose of IRDM patients with CAD was 0.74 units/kg in males and 1.3 units/kg in females and those without CAD was 0.30 units/kg in males and 0.73 units/kg in females. There was no significant difference in the prevalence of hypertension, dyslipidemia and nephropathy between the patients with or without CAD. All the three IRDM males with CAD had BMI less than 25 kg/m 2 where as both the IRDM females with CAD had BMI greater than 25 kg/m 2 . Both the IRDM females with CAD had CAD before institution of insulin therapy, though they ultimately required higher insulin dose denoting higher degree of insulin resistance(IR) and suggesting non-contribution of insulin therapy in the pathogenesis of CAD. Conclusion This study highlights a)higher incidence of CAD in IRDM patients, b)higher insulin requirement in CAD patients,c)higher insulin dose in females as compared to males and d)females(all obese)having CAD earlier than males,having CAD before insulin therapy but requiring higher dose than non-CAD females. These could be due to a) insulin deficiency and predominantly IR impacting IRDM[3];b)IR enhancing atherosclerosis((through proinflammatory cytokines, oxidant stress and procoagulant activity (not measured)promoting CAD[2,3,4,]);c)higher BMI[6] and associated greater IR[3] contributing to higher insulin dose in females, though,they required insulin much later;some studies have shown female gender having a protective effect on insulin initiation[5];d)the overlap of traditional CV risk factors viz. dyslipidemia,hypertension, nephropathy in IRDM and non-IRDM patients with or without CAD points towards the predominant contribution of proinflammatory cytokines viz CRP and procoagulants viz . PAI in the aetiopathogenesis of CAD[4]. Further studies on larger patient population are required to substantiate these observations.

Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria

Introduction: Tropical calcific pancreatitis is known to be associated with malnutrition and insulin-requiring diabetes mellitus. Recent studies suggest that genetic and environmental factors play a role in its etiopathogenesis. Objective: The objectives of this was were to study the prevalence, profile, and outcome of children managed for type 1 diabetes mellitus with pancreatic calcification. Materials and Methods: This was a cross-sectional study of children managed for type 1 diabetes mellitus in the pediatric endocrine unit of Federal Teaching Hospital Abakaliki, Nigeria. All patients who consented underwent ultrasonography of the pancreas. We undertook a case note review to identify factors that may be associated with pancreatic calcification. Results: Thirty-seven children were diagnosed with diabetes mellitus. The mean age was 12.3 years (5–17 years), 21 males and 16 females. Twenty of 37 (54.1%) patients were screened for pancreatic calcifications using abdominal ultrasound. Seventeen of 37 were not studied as nine of them (24.3%) died, six lost to follow-up, and two declined to participate. The mean duration of diabetes mellitus was 2.7 years (3 months–8 years). All patients were managed with a premixed twice-daily insulin regimen. Pancreatic calcification was seen in seven out of the 20 (35%) and was commoner among males and older children. The average glycosylated hemoglobin (Hba1c) was 13 and 11, and average height/weight standard deviation score was –1.9/–1.9 and –1.03/–1.02 in those with calcification and those without, respectively. Conclusion: Tropical calcific pancreatitis is common among children diagnosed with diabetes mellitus in Abakaliki, Nigeria and is associated with morbidity. Routine pancreatic ultrasound of patients with type 1 diabetes mellitus may be necessary.

Marked Hypoleptinemia precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> The development of immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation has revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI use, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and rarely hypoparathyroidism, are increasing. Lipodystrophy, presumably due to autoimmune destruction of adipocytes, leading to metabolic complications is a less well recognized adverse effect of ICI therapy. <h3>Objective/Purpose</h3> To report the clinical features and evolution of Acquired Generalized Lipodystrophy (AGL) in a patient on ICI therapy. <h3>Methods</h3> Case Report: A 66-year-old woman with metastatic lung adenocarcinoma was started on combination chemo/immunotherapy with programmed cell death-1 (PD-1) inhibitor- pembrolizumab after surgical resection of cerebellar mass and radiation. She had good tumor response but developed primary hypothyroidism and secondary adrenal insufficiency approximately ten months after initiation of ICI. <h3>Results</h3> Approximately 15 months following the treatment, she developed new-onset insulin requiring diabetes mellitus but without autoantibodies associated with type 1 diabetes. At that time, she was also noted to have hypertriglyceridemia (436 mg/dL), and elevated liver enzymes (3-4 X ULN), and a subsequent liver biopsy revealed severe macrovesicular steatosis. Her BMI was 30 kg/m2 and she had mild loss of buccal fat. Skin fold thickness measurements over the trunk and limbs were in the normal range. However, she had an undetectable serum leptin level and whole body fluorodeoxyglucose (FDG)- positron emission tomography (PET) scan, obtained for cancer surveillance, showed mild diffuse FDG activity throughout the subcutaneous tissues. She was advised low fat diet and started on insulin therapy. Over the next three months, she lost about 20 kg weight with generalized loss of subcutaneous fat from face, trunk, and extremities. Pioglitazone was started but discontinued after 4 weeks due to pedal edema and no effect on fat loss. Despite generalized lipodystrophy, she has maintained good glucose control on moderate dose insulin therapy (0.6 â€" 0.8 units/kg) and with normalization of liver enzymes and serum triglycerides. <h3>Conclusions</h3> ICI therapy can be associated with AGL, and the diagnosis must be considered in patients who develop metabolic complications such as diabetes, dyslipidemia, or steatohepatitis. Interestingly, metabolic abnormalities may precede overt fat loss. Hypoleptinemia and diffuse FDG uptake of subcutaneous tissue suggest subclinical panniculitis and adipocyte dysfunction even before clinically evident lipodystrophy.

Challenges of Telemonitoring Programs for Complex Chronic Conditions: Randomized Controlled Trial With an Embedded Qualitative Study.

BackgroundDespite the growing prevalence of people with complex conditions and evidence of the positive impact of telemonitoring for single conditions, little research exists on telemonitoring for this population.ObjectiveThis randomized controlled trial and embedded qualitative study aims to evaluate the impact on and experiences of patients and health care providers (HCPs) using a telemonitoring system with decision support to manage patients with complex conditions, including those with multiple chronic conditions, compared with the standard of care.MethodsA pragmatic, unblinded, 6-month randomized controlled trial sought to recruit 146 patients with ≥1 diagnosis of heart failure (HF), uncontrolled hypertension (HT), and insulin-requiring diabetes mellitus (DM) from outpatient specialty settings in Toronto, Ontario, Canada. Participants were randomized into the control and telemonitoring groups, with the latter being instructed to take readings relevant to their conditions. The telemonitoring system contained an algorithm that generated decision support in the form of actionable self-care directives to patients and alerts to HCPs. The primary outcome was health status (36-Item Short Form Health Survey questionnaire). Secondary outcomes included anxiety and depression, self-efficacy in chronic disease management, and self-reported health service use. HF-related quality of life and self-care measures were also collected from patients followed for HF. Within- and between-group change scores were analyzed for statistical significance (P<.05). A convenience sample of HCPs and patients in the intervention group was interviewed about their experiences.ResultsA total of 96 patients were recruited and randomized. Recruitment was terminated early because of implementation challenges and the onset of the COVID-19 pandemic. No significant within- and between-group differences were found for the main primary and secondary outcomes. However, a within-group analysis of patients with HF found improvements in self-care maintenance (P=.04) and physical quality of life (P=.046). Opinions expressed by the 5 HCPs and 13 patients who were interviewed differed based on the monitored conditions. Although patients with HF reported benefitting from actionable self-care guidance and meaningful interactions with their HCPs, patient and HCP users of the DM and HT modules did not think telemonitoring improved the clinical management of those conditions to the same degree. These differing experiences were largely attributed to the siloed nature of specialty care and the design of the decision support, whereby fluctuations in the status of HT and DM typically required less urgent interventions compared with patients with HF.ConclusionsWe recommend that future research conceive telemonitoring as a program and that self-management and clinical decision support are necessary but not sufficient components of such programs for patients with complex conditions and lower acuity. We conclude that telemonitoring for patients with complex conditions or within multidisciplinary care settings may be best operationalized through nurse-led models of care.Trial RegistrationClinicalTrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852International Registered Report Identifier (IRRID)RR2-10.2196/resprot.8367

Maternal body mass index and country of birth in relation to the adverse outcomes of large for gestational age and gestational diabetes mellitus in a retrospective cohort of Australian pregnant women

BackgroundThe prevalence of gestational diabetes mellitus in Australia has been rising in line with the increased incidence of maternal overweight and obesity. Women with gestational diabetes mellitus, high body mass index or both are at an elevated risk of birthing a large for gestational age infant. The aim was to explore the relationship between country of birth, maternal body mass index with large for gestational age, and gestational diabetes mellitus. In addition to provide additional information for clinicians when making a risk assessment for large for gestational age babies.MethodA retrospective cohort study of 27,814 women residing in Australia but born in other countries, who gave birth to a singleton infant between 2008 and 2017 was undertaken. Logistic regression analysis was used to examine the association between the aforementioned variables.ResultsA significantly higher proportion of large for gestational age infants was born to overweight and obese women compared to those who were classified as underweight and healthy weight. Asian-born women residing in Australia, with a body mass index of ≥40 kg/m2, had an adjusted odds ratio of 9.926 (3.859–25.535) for birthing a large for gestational age infant. Conversely, Australian-born women with a body mass index of ≥40 kg/m2 had an adjusted odds ratio of 2.661 (2.256–3.139) for the same outcome. Women born in Australia were at high risk of birthing a large for gestational age infant in the presence of insulin-requiring gestational diabetes mellitus, but this risk was not significant for those with the diet-controlled type. Asian-born women did not present an elevated risk of birthing a large for gestational age infant, in either the diet controlled, or insulin requiring gestational diabetes mellitus groups.ConclusionsWomen who are overweight or obese, and considering a pregnancy, are encouraged to seek culturally appropriate nutrition and weight management advice during the periconception period to reduce their risk of adverse outcomes.

Multiple Challenges: An Unusual Case of an Adrenal Mass With Plurihormonal Secretion of Catecholamines and Cortisol in a Patient With Several Neoplasms

Introduction:Simultaneous hypersecretion of both catecholamines and cortisol in one adrenal tumor is rarely seen because cortical cells, which produce cortisol, and medullary cells, which secrete catecholamines, are derived from different germ layers1. Formidable challenges ensue from a tumor with a complex behavior. We demonstrate here the clinical course and multi-modal management of the case of an adrenocortical adenoma which had neuroendocrine differentiation accounting for the excess of both catecholamine and cortisol hormones in a patient with multiple neoplasms.Clinical Case: An adrenal mass was incidentally discovered in a 61-year old female undergoing imaging as part of the metastatic work-up for an esophageal mass. The patient has insulin-requiring diabetes mellitus, hypertension and a history of breast cancer. A right adrenal gland mass, avidly enhancing, measuring 3.8 x 2.7 x 2.7 cm was found on abdominal imaging. The 24-hour urine metanephrine collections were done, and these were more than twice elevated in two instances at 2.516 mg/24 hours and 2.101 mg/24 hours (NV: 0–1 mg/24 hours). An unsuppressed cortisol level at 6.57 μg/dL (NV: ≤ 1.8 μg/dL) was obtained after the 1 mg dexamethasone suppression test. Hypercortisolism was confirmed with an elevated 24-hour urine free cortisol at 312.07 μg/24 hours (NV: 20–90 μg/24 hours). Adrenocorticotrophic hormone (ACTH) was low at 0.90 pg/ml, indicative of the presence of an adrenal form of Cushing’s. Primary aldosteronism was ruled out based on a ratio between plasma aldosterone concentration and plasma renin activity of less than 20.Pre-operative alpha blockade with terazosin was initiated. Right adrenalectomy was done. Histopathology revealed an adrenal mass of cortical origin, atypically staining positively for synaptophysin, which is indicative of neuroendocrine differentiation of the tumor. The patient had better blood pressure and glycemic control after the adrenalectomy.Clinical Lessons: An adrenocortical adenoma very seldom undergoes neuroendocrine differentiation. Pathophysiologic mechanisms include a genetic aberration in cortical cells leading to production of catecholamines2. This case underscores the importance of a comprehensive biochemical evaluation of a patient with an adrenal mass because control of hormonal hypersecretion is essential in reducing cardiovascular risks, morbidity and mortality.

Glycogenic Hepatopathy in a Patient with Pancreatogenic Diabetes

Glycogenic hepatopathy is characterized by acute liver injury secondary to reversible accumulation of excess glycogen in hepatocytes. This phenomenon has been described in type 1 diabetes, with few cases reported in patients with type 2 diabetes. Glycogenic hepatopathy in the setting of pancreatogenic (type 3c) diabetes has yet to be reported.A 57-year-old female with a history of insulin-requiring pancreatogenic diabetes mellitus secondary to alcohol-induced chronic pancreatitis status post distal pancreatectomy presented with recurrent admissions for abdominal pain, hyperglycemia, hyperosmolar hyperglycemic state (HHS), and unexplained elevation of liver transaminase levels. Glycemic control remained poor over many years with consistently elevated HbA1c in the setting of labile blood sugars, medication noncompliance, and lifestyle non-adherence.The patient was admitted to the hospital with altered mental status and markedly elevated blood glucose (1,182 mg/dL) concerning for HHS. On admission, her liver function tests (LFTs) revealed elevated alkaline phosphatase (1,011 U/L, n <150 U/L), AST (583 U/L, n <34 U/L), and ALT (517 U/L, n <55 U/L). Direct and total bilirubin were within normal limits. The patient underwent extensive workup including drug and toxin levels, autoimmune evaluation, serology for infectious causes, abdominal computed tomography scanning, right upper quadrant ultrasound, and magnetic resonance cholangiopancreatography (MRCP). All laboratory workup was negative, ultrasound was unremarkable, and MRCP showed no evidence of biliary or common bile duct dilatation. Throughout her hospitalization, LFTs gradually improved with optimization of blood glucose.Less than one week later, the patient returned with blood glucose of 673 mg/dL and LFTs notable for alkaline phosphatase 789 U/L, AST 1,068 U/L, and ALT 299 U/L. Again, all testing was negative for causes of rapid increase in liver enzymes. Similar to previous admissions, her LFTs improved with resolution of hyperglycemia. Review of electronic medical record revealed a similar trend during previous admissions. The patient did not undergo liver biopsy; however, the parallel relationship of LFTs and hyperglycemia, in the absence of radiologic or laboratory evidence of alternate liver pathology, supports the diagnosis of glycogenic hepatopathy.This is the first case of glycogenic hepatopathy reported in a patient with pancreatogenic diabetes. Due to the rarity of this condition and minimal literature of its occurrence in adult non-type-1 diabetics, glycogenic hepatopathy is likely infrequently considered when evaluating patients with recurrent hyperglycemia and elevated LFTs. This case accentuates the need for further research of this condition in non-type 1 diabetics as the prognosis and management differ from other forms of acute liver injury.

Temporal Trends in Patient Risk Profile and Clinical Outcomes Following Percutaneous Coronary Intervention

BackgroundPatient selection and procedural characteristics continue to evolve in percutaneous coronary intervention (PCI). Australian data on long-term trends and outcomes are limited. This study aimed to identify long-term temporal trends in patient characteristics and outcomes in a large Australian PCI cohort. MethodsWe analysed data from 41,146 PCI procedures included in the multi-centre Melbourne Interventional Group registry to determine trends in patient characteristics, procedural practices and outcomes from 2005 to 2018. Procedures were divided into 2-yearly periods for trends analysis. ResultsTemporal trends in patient characteristics showed increases in age, proportion of males, rates of obesity, insulin-requiring diabetes mellitus, current smoking, obstructive sleep apnoea and prior PCI (all Ptrend < 0.01). Increases in the proportion of ST-elevation myocardial infarction, cardiogenic shock or out-of-hospital cardiac arrest (OHCA) were observed, and CathPCI National Cardiovascular Data Registry mortality risk scores increased over time (all Ptrend < 0.01). Use of radial access and drug-eluting stents increased, and lesions treated were more frequently ostial, left main or ACC/AHA type B2/C in recent years (all Ptrend < 0.01). In contrast, major bleeding and no reflow rates declined, however 30-day mortality, 12-month mortality and rates of stroke increased (all Ptrend < 0.01). Rates of vascular complications and 30-day target vessel revascularisation remained similar. In multivariable analysis, 2-yearly time periods were not independently associated with risk of 30-day mortality or 30-day MACE. ConclusionsOver the last 14 years, Australian PCI procedural complexity and patient risk profiles have increased. Higher mortality rates appear to relate to increased patient risk profile rather than procedural factors.

The effect of an educational intervention on the metabolic control of diabetic patients

Diabetic patients have a poor adherence to lifestyle changes and a low compliance with medications. To study the effect of an educational intervention on the metabolic control of patients with diabetes mellitus. We studied insulin requiring diabetic patients attended at a primary health care clinic, who were randomly divided in two groups. One group participated in four modules of an educative intervention, carried out in four occasions. The other group did not participate in the educational sessions. Clinical, anthropometric and laboratory variables of the participants were obtained from their medical records, at three and six months after the intervention. We recruited 22 men aged 64 ± 14 years and 48 women aged 63 ± 10 years. Thirty-six of these received the educational intervention. Eighty four percent were overweight or obese. The proportion of compensated patients, defined as those having a glycosylated hemoglobin between 7 and 9%, increased significantly after the educational intervention (χ2 = 7.9 p < 0.01, odds ratio: 0.2). A educational intervention in patients with insulin requiring diabetes mellitus improved the metabolic control of their disease.

Blood glucose level impact on biometric parameters, refraction and intraocular pressure in patients with subcompensated insulin-requiring type II diabetes

Purpose. To study the relationship of biometric parameters, visual acuity, eye refraction and intraocular pressure (IOP) with blood glucose levels and glycated hemoglobin (HbA1c) in patients with subcompensated insulin-requiring type II diabetes mellitus. Material and methods. Ophthalmic monitoring lasted 3 years, the experience of insulin therapy — 6 years. 32 patients (27 women and 5 men) with insulin-requiring diabetes mellitus and no severe general diabetic complications or concomitant eye pathology were monitored for 3 years. The patients’ average age was 60.4 ± 5.3 years; average weight 94.3 ± 16.5 kg; average height 163.4 cm; average BMI (body mass index) was 29.93 kg/m2, all received insulin treatment for 6 years. Patients determined the level of blood glucose themselves on a daily basis using individual “Accu-Check” and/or “OneTouch select” glucometers, supplemented by endocrinologist checks on scheduled examinations once a month. The level of glycated hemoglobin (HbA1c) was determined once every 3–6 months. The 3-year ophthalmic monitoring involved both eyes and included biomicroscopy, autorefractometry, pneumotonometry, measurement of the anterior-posterior axis, the depth of the anterior chamber and lens thickness; pachymetry of the cornea in the central optical zone, and ophthalmoscopy. Visometry was performed according to ETDRS (Early Treatment Diabetic Retinopathy Study Research Group) requirements. Results. The impact of blood glucose level on visual acuity (Spearman R = 0.18/-0.23, t (N-2) = 1.07/-1.34, p = 0.1) is higher than that of HbA1c (Spearman R = 0.07/-0.15, t (N-2) = 0.4/-0.8, p = 0.65) The higher the glucose level, the lower the depth of the anterior chamber and the shorter the APA. In contrast, the higher the level of HbA1c, the thicker the cornea in the central optical zone. Both the glucose and the HbA1c levels reveal a similar positive correlations with IOP. A refraction shift toward myopia from 42 % to 55 % was shown to correlate to HbA1c, and a corresponding reduction of hyperopia share was revealed. Conclusions. In patients with subcompensated insulin-requiring diabetes mellitus type II, biometric parameters, refraction and intraocular pressure are determined by changes in the level of blood glycemia.

New-onset insulin-dependent diabetes due to nivolumab.

SummaryNivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.Learning points:Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study

ObjectiveWomen with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes. MethodsWomen with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month observation period (EudraCT: 2007-000634-39). Both groups received lifestyle counseling. The primary efficacy outcomes were the diagnosis of diabetes (American Diabetes Association (ADA) criteria) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT). ResultsBetween 2008 and 2015, 113 patients (58 vildagliptin, 55 placebo) were randomized within 2.2–10.4 (median 8.6) months after delivery. At the interim analysis, nine diabetic events and 28 IFG/IGT events had occurred. Fifty-two women withdrew before completing the treatment phase. Because of the low diabetes rate, the study was terminated. Lifestyle adherence was similar in both groups. At 24 months, the cumulative probability of postpartum diabetes was 3% and 5% (hazard ratio: 1.03; 95% confidence interval: 0.15–7.36) and IFG/IGT was 43% and 22% (hazard ratio: 0.55; 95% confidence interval: 0.26–1.19) in the placebo and vildagliptin groups, respectively. Vildagliptin was well tolerated with no unexpected adverse events. ConclusionsThe study did not show significant superiority of vildagliptin over placebo in terms of reducing the risk of postpartum diabetes. However, treatment was safe and suggested some improvements in glycemic control, insulin resistance, and β-cell function. The study identified critical issues in performing clinical trials in the early postpartum period in women with GDM hampering efficacy assessments. With this knowledge, we have set a basis for which properly powered trials could be performed in women with recent GDM. Trial registration number at ClinicalTrials.govNCT01018602.

Sex differences in left main coronary artery stenting: Different characteristics but similar outcomes for women compared with men

BackgroundThe clinical outcomes for women compared with men undergoing left main PCI were sparse. We compared the characteristics and long-term outcomes in women versus men after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main CAD. MethodsWe identified 2328 patients (545 women; 1783 men) with unprotected left main CAD who received PCI with DES between January 2007 and December 2013 in the Interventional Cardiology Research In-cooperation Society-left MAIN revascularization (IRIS-MAIN) registry. The primary outcome was a composite of death from any cause, myocardial infarction, or stroke. ResultsThe median follow-up time was 2.9years (interquartile range: 1.0–4.1years). Women were older, had a higher incidence of insulin-requiring diabetes mellitus and hypertension, and more commonly presented with acute coronary syndrome than men. Left main ostial lesion was more common in women, whereas left main bifurcation lesion with more extensive CAD was more common in men. The incidence of primary outcome was similar between the two groups (10.8% vs. 10.8%, respectively, log-rank p=0.587). The results were similar after adjustment for baseline variables and consistent across major subgroups. The need for target lesion revascularization was significantly higher in women than in men (8.8% vs. 5.7%, respectively, p<0.05) but the sex bias was not confirmed after adjusting for confounders. ConclusionsWomen, as compared to men, had different clinical and lesion characteristics but similar long-term outcomes after PCI with DES for left main CAD.

616: Association between ultrasonographic estimated fetal weight and the risk of cesarean delivery among nulliparous women with diabetes mellitus

Prior work assessing the relationship between third trimester ultrasound estimate of fetal weight (US-EFW) and cesarean delivery (CD) risk has excluded women with diabetes mellitus (DM), who are at higher risk of CD than their counterparts without DM. Our aim was to examine the association between having an US-EFW as well as a predicted large-for-gestational-age (LGA) US-EFW and mode of delivery among nulliparous women with DM. This is a retrospective cohort of nulliparous women with gestational A2 DM or pre-existing DM who delivered term, singleton gestations at a single academic institution (2010-15). Clinical and demographic data were abstracted to determine 1) whether having had an US-EFW within 5 weeks of delivery was associated with any CD and with CD for arrest of dilation, descent, or failed induction of labor (arrest disorder, AD) and 2) among those with a recent US-EFW, whether an LGA diagnosis was associated with any CD and with CD for an AD. We used bivariable analyses and multivariable logistic regression as appropriate. Of 316 women who met eligibility criteria, 242 (76.6%) had an US-EFW within 5 weeks of delivery. Women who had an US-EFW were younger, had greater BMI, were more likely to have pre-existing DM, were more likely to undergo induction of labor, and ultimately had neonates with greater birthweight, but were not different by gestational age at delivery. Having a recent US-EFW was associated with increased frequency of any CD (53.7% vs. 28.4%, p< 0.001); this finding persisted even when controlling for birthweight and other confounding factors (aOR 2.52, 95% CI 1.33-4.77) (Table). Among those with a recent US-EFW, diagnosis of LGA was associated with any CD (69.7% vs. 46.4%, p=0.001) and with CD for an arrest disorder (61.8% vs. 28.3%, p< 0.001), but in multivariable models that accounted for birthweight and other potential confounding factors, only the relationship with CD for an AD persisted (aOR 2.23, 95%CI 1.07-4.68) (Table). The performance of an US-EFW among nulliparous women with insulin-requiring DM was associated with an increased risk of CD. Moreover, an ultrasound diagnosis of LGA was associated with an increased risk of CD for an AD. These associations persisted even after controlling for birthweight.

Impact of Diabetes Mellitus on Clinical Characteristics, Management, and In-hospital Outcomes in Patients With Acute Myocardial Infarction (from the NCDR)

Patients with diabetes mellitus (DM) presenting with acute myocardial infarction (AMI) have worse outcomes versus those without DM. Comparative contemporary data in patients presenting with AMI with insulin-requiring diabetes mellitus (IRDM), noninsulin-requiring diabetes mellitus (NIRDM), and newly identified DM (hemoglobin A1C level >6.5%) versus patients without DM are limited. This observational study from the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (ACTION Registry-GWTG consisted of 243,861 patients with AMI from 462 US sites identified from January 2007 to March 2011 entered into the registry. Clinical characteristics, management, and in-hospital outcomes were analyzed. Patients with DM with non-ST-segment elevation myocardial infarction (NSTEMI; n = 53,094, 35%) were less likely to undergo diagnostic angiography or revascularization, whereas those with ST-segment elevation myocardial infarction (STEMI) (n = 21,507, 23%) were less likely to undergo reperfusion therapy compared with patients without DM. There was an increased adjusted risk of in-hospital mortality in the DM group in both the NSTEMI (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.06 to 1.22) and STEMI (OR 1.17, 95% CI 1.07 to 1.27) population. In patients with DM, the risk-adjusted in-hospital mortality was higher in patients with IRDM than those with NIRDM in the NSTEMI group (OR 1.12, 95% CI 1.01 to 1.24) but not in the STEMI group (OR 1.12, 95% CI 0.95 to 1.32). Newly diagnosed patients with DM presenting with AMI had similar unadjusted in-hospital outcomes compared with patients without DM. In conclusion, patients with DM presenting with AMI have a higher mortality risk than patients without DM. In patients with DM, those with IRDM presenting with NSTEMI had an increased mortality than those with NIRDM.

Post cardiac surgery acute kidney injury: a woebegone status rejuvenated by the novel biomarkers.

Background:Acute kidney injury (AKI) is common after cardiac surgery, the incidence varying between 7.7% and 28.1%. It significantly increases morbidity and mortality. Creatinine considerably delays the diagnosis with its own attended demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis thus reducing the morbidity and mortality. Biomarkers of our study were neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18).Objectives:To find out the incidence of AKI in post-cardiac surgery patients in our hospital, the ability of the two biomarkers in early diagnosis in predicting the severity of AKI based on RIFLE’s criteria and their ability to discriminate pre-renal from intrinsic AKI.Patients and Methods:One-hundred patients who underwent cardiac surgery were selected. Midstream urine samples were collected at 3 time intervals (baseline before surgery, 24 hours and 7 days after surgery). Biomarkers were measured by ELISA using BIORAD processors. Fractional excretion of sodium and urea were used to discriminate pre-renal from intrinsic AKI.Results:Out of 100 patients, 31 had AKI, 11 being pre-renal and 20 intrinsic AKI. Four patients required renal replacement therapy (12.9% among AKI cases and 4% in the overall study cohort). Four among 31 expired in intensive care unit. Identifiable risk factors for AKI included insulin requiring diabetes mellitus, chronic obstructive pulmonary disease, increased cardio-pulmonary bypass time, combined valvular surgery and coronary artery bypass grafting, employment of intra-aortic balloon counter pulsation, left main coronary artery occlusion and an ejection fraction of < 40%. NGAL was extremely sensitive (area under curve-0.96) in detecting intrinsic AKI at 24 hours followed by IL-18 ratio with an area under curve of 0.89. Creatinine at 24 hours was able to detect only 31.6% of intrinsic AKI. None of the pre-renal cases showed rise in the urinary biomarker levels. Patients with higher stages of AKI had higher levels of both biomarkers than those at lower stages.Conclusions:NGAL and IL-18 obviated the disadvantages of creatinine. They were efficient in early detection of AKI, in differentiating pre-renal from intrinsic AKI and in predicting the severity of AKI reliably in post-cardiac surgery patients.