Marc Rendell

The Rose Salter Medical Research Foundation · Diabetes

The nested wave hypothesis proposes a resolution to the long-standing puzzle of quantum entanglement and its apparent incompatibility with the principles of special relativity. By introducing a subluminal mediating wave (Wave 1) that interacts with entangled particles (modeled as quantum harmonic oscillators, or QHOs), the hypothesis provides a phy...

The nested wave hypothesis proposes a resolution to the long-standing puzzle of quantum entanglement and its apparent incompatibility with the principles of special relativity. (Wave 1) that interacts with entangled particles (modeled as quantum harmonic oscillators, or QHOs), the hypothesis provides a physically intuitive and mathematically consis...

The nested wave hypothesis proposes a resolution to the long-standing puzzle of quantum entanglement and its apparent incompatibility with the principles of special relativity. By introducing a subluminal mediating wave (Wave 1) that interacts with entangled particles (modeled as quantum harmonic oscillators, or QHOs), the hypothesis provides a phy...

We propose a nested wave model to address this nonlocal behavior without abandoning the fundamental principles of relativity. Our model introduces a hidden wave structure (Wave 2) interacting with conventional wavefunctions (Wave 1). As entangled particles separate by significant distances, new nested wave structures emerge within Wave 2 to mediate...

A cohort of 30,423 Covid-19 patients treated between March 2020 and December 2021 at the IHU-Méditerranée Infection in Marseille (France) was retrospectively analyzed in terms of treatment attempted and disease worsening factors to quantify efficacy with respect to the composite endpoint of transfer to intensive care unit or death, within a couple...

A cohort of 30,423 Covid-19 patients treated between March 2020 and December 2021 at the IHU-Méditerranée Infection in Marseille (France) was retrospectively analyzed in terms of treatment attempted and disease worsening factors to quantify vaccination efficacy with respect to the composite endpoint of transfer to intensive care unit or death, with...

Introduction Obesity is a key target in the treatment and prevention of diabetes and independently to reduce the burden of cardiovascular disease. We reviewed the options now available and anticipated to deal with obesity. Areas covered We considered the epidemiology, genetics, and causation of obesity and the relationship to diabetes, and the die...

Introduction In the last several decades, fueled by gene knockout and knockdown techniques, there has been substantial progress in detailing the pathways of gluconeogenesis. A host of molecules have been identified as potential targets for therapeutic intervention. A number of hormones, enzymes and transcription factors participate in gluconeogenes...

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, p...

COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing...

Background: Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). Methods: We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search t...

Introduction: 'Prediabetes' is a condition of elevated glucose not attaining the established criteria for a diagnosis of diabetes. The United States Diabetes Prevention Program (DPP) began in 1996 and was the iconic study of prediabetes. In that study, after 3 years, the risk of reaching the numerical criteria of diabetes was reduced by 58% by int...

Background. The spread of COVID-19 from Wuhan in China throughout the world has been alamingly rapid. Epidemiologic techniques succeeded in containing the disease in China, but efforts were not as successful in the rest of the world, particularly the United States where there have been 1,592, 599 cases with 95,863 deaths as of May 25, 2020. Project...

In the accompanying article, Goldenberg et al review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5 fold increase in risk of DKA in type 1 diabetes patients treated with SGLT2 inhibitors. They have a number of suggestions to attempt to mitigate the risk of DKA in type 1 patients treate...

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary cancer syndrome that results from mutations in several genes, including the CDKN2A gene. In addition to melanoma, certain other malignancies such as pancreatic cancer are known to occur more frequently in family members who carry the mutation. However, as these families have...

Gene knockout has been a powerful technique to evaluate the physiologic role of selected gene products. Lexicon pioneered high-throughput gene knockout technology and went further in designing agents to inhibit products of gene expression. Two agents have entered late-stage development. Telotristat is an inhibitor of tryptophan hydroxylase (TPH), p...

Introduction: Although premixed fixed ratio NPH insulin products are commonly used in type 2 diabetes patients, the advent of Glargine insulin which cannot be formulated together with a rapid acting insulin (basal-bolus) has largely eliminated premixed insulin from use in type 1 diabetes. Degludec insulin can be formulated together with Aspart insu...

Introduction: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. The agent blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1. Initial studies were directed at type 1 diabetes. Areas covered: The published information on so...

Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical o...

Aims To compare the efficacy and safety of MK‐1293 insulin glargine (Mk‐Gla) and Lantus (Sa‐Gla) in people with type 2 diabetes mellitus (T2DM). Materials and Methods This Phase 3, randomized, active‐controlled, open‐label, 24‐week clinical trial enrolled 531 participants with T2DM (HbA1c ≤11.0%) eligible for or currently taking basal insulin (≥10...

Introduction: Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection and approved for use in type 2 diabetes. It has less gastrointestinal side effects than other GLP-1 RAs in current use but does not improve HbA1c or promote weight loss to the same extent as some competitor agents. Area covered: The current...

INTRODUCTION: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased g...

Introduction: Albiglutide is a marketed long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. It has significantly less gastrointestinal side effects than other GLP-1 RAs in current use but does not improve HbA1c or promote weight loss to the same extent as competitor agents such as liraglutide. Area Covered: The safety of...

Aims Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. Methods Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or plac...

Insulin degludec has been the product of a sophisticated and systematic biochemical engineering program which began with the release of insulin detemir. The goal was to produce a long-lasting basal insulin with low individual variability. Certainly, this goal has been achieved. Degludec has a duration of action approaching twice that of glargine. A...

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM. Methods: Integrated safety analysis included seven phase-3 T2DM studie...

Introduction: Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. Area Covered: The pharmacokinetic and pharmacodynamic properties of albiglutide and its clinical effects are discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administra...

In this issue of Cancer Research, Almassalha and colleagues have proposed a new concept of the development of malignancy, that of the greater genomic landscape. They propose a stressor-related exploration of intracellular genomic sites as a response mechanism. This process can express sites with beneficial or deleterious effects, among them those t...

Background: Point-of-care (POC) testing of HbA1c is used as a time-efficient tool to improve treatment and management planning for diabetes in the clinic setting. HbA1c values are the basis for monitoring ongoing response to treatment and to make adjustments to diabetes therapy. Yet, there is ongoing controversy as to the accuracy of POC assays. D...

Aims/hypothesis: Additional safe and effective therapies for type 2 diabetes are needed, especially ones that do not cause weight gain and have a low risk of hypoglycaemia. The present study evaluated albiglutide as monotherapy. Methods: In this placebo-controlled study, 309 patients (aged ≥ 18 years) with type 2 diabetes inadequately controlled...

Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature sear...

Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by autoreactive effector T cells. We hypothesized that a combination of targeted depletion and modulation of effector T cell activity by alefacept would result in prolonged preservation of endogenous insulin secretion in patients with newly diagnosed T1D. In a multicenter, rand...

Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly d...

There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the...

To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes. We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control,...

Glucagon-like polypeptide (GLP-1) receptor agonist treatment has multiple effects on glucose metabolism, supports the β cell, and promotes weight loss. There are now five GLP-1 agonists in clinical use with more in development. GLP-1 treatment typically can induce a lowering of hemoglobin A1c (HbA1c) of 0.5-1.5% over time with weight loss of 2-5%....

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When oral hypoglycemic agents do not successfully suppress hyperglycemia, the traditional approach has been to add insulin injections. With the coming of glucagon-like peptide 1 (GLP-1) receptor agonists carrying the benefits of weight loss and reduced risk of hypoglycemia, it has been suggested that GLP-1 agents should be used instead. There is eq...

Introduction: Dipeptidyl peptidase inhibitors (DPP-4-i) are highly selective inhibitors of the enzyme DPP-4. They act by increasing levels of incretin hormones, which have potent effects on insulin and glucagon release, gastric emptying, and satiety. Our goal is to review the safety issues related to DPP-4-i. Areas covered: This review is based...

Technosphere® insulin uses a unique carrier -fumaryl diketopiperazine (FDKP)- which adsorbs insulin to form microparticles to permit delivery to the alveoli by inhalation. Toxicity studies have been entirely negative. The pulmonary absorption of insulin is very rapid, and the disappearance time is shorter than for subcutaneously delivered rapid-act...

The American Diabetes Association and The Endocrine Society workgroup on the 2013 classification of hypoglycemia (1) in patients with diabetes changed the previously used term “relative hypoglycemia” to “pseudo-hypoglycemia” while defining symptoms of hypoglycemia without confirmatory low glucose values and failing to include falsely low readings o...

Diabetes is an ever increasing health problem in our society. Due to associated small and large vessel conditions, patients with diabetes are two- to four-fold more likely to require hospitalization than nondiabetic individuals. Furthermore, hyperglycemia in hospitalized patients results in increased susceptibility to wound infections, worse outcom...

Background: Type 1 diabetes results from autoimmune targeting of the pancreatic β cells, likely mediated by effector memory T (Tem) cells. CD2, a T cell surface protein highly expressed on Tem cells, is targeted by the fusion protein alefacept, depleting Tem cells and central memory T (Tcm) cells. We postulated that alefacept would arrest autoimmu...

In Reply We appreciate the clarifications regarding this particular use of contraception and the Jewish religion. As we stated in our Viewpoint, there are many shared beliefs regarding birth control among the major religions, as well as certain specific differences, but the focus of our article was not so much about the morality of artificial means...

Atherosclerotic cardiovascular disease (CVD) is the number one cause of death globally, and lipid modification, particularly lowering of low density lipoprotein cholesterol (LDLc), is one of the cornerstones of prevention and treatment. However, even after lowering of LDLc to conventional goals, a sizeable number of patients continue to suffer card...

Insulin degludec is, like insulin detemir, a product of coupling of Des-B30 threonine insulin to fatty acid side chains. After injection, degludec self associates, precipitating in subcutaneous tissue. There is a continuous and highly predictable slow dissociation of insulin monomers from this depot; insulin levels rise immediately reaching tmax at...

The Obama Administration and the Catholic Church are in conflict over the implementation of provisions of the Patient Protection and Affordable Care Act (HR 3590) requiring that all US Food and Drug Administration–approved contraceptive agents, not including abortifacients but including so-called morning after pills and sterilization procedures, be...

Over the past 20 years, the treatment armamentarium for diabetes has greatly expanded: There are now many different classes of non-insulin drugs and many types of both long-and short-acting insulin now available. The newer classes of agents include disaccharidase inhibitors, thiazolidinediones, meglitinides, glucagon-like peptide one analogs, and d...

Introduction: In 2009, several epidemiological studies suggested a higher frequency of malignancy in insulin glargine -treated patients. A number of follow-up epidemiological population studies as well as two randomized, controlled clinical studies, one a 5000-patient retinopathy study and the other a 12,000-patient cardiovascular outcomes trial (...

Introduction: The evaluation of agents to treat elevated blood glucose is straightforward and is accomplished with short duration studies, but it is more difficult to demonstrate safety of these agents over long periods of clinical use. Numerous large studies have raised questions as to the cardiovascular risks of certain drugs such as the thiazol...

The cutaneous hyperemic response following the release of direct pressure occlusion lasts much longer than the short-term hyperemia that occurs after proximal arterial occlusion. Post-pressure hyperemia may be an important mechanism to prevent pressure induced injury to the skin. The role of vasoactive mediators in modulating post-pressure hyperemi...

The USPTSF bases its recommendation, in large part, on the 2 largest published randomized clinical trials (2). The U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial randomly assigned 76 685 men aged 55 to 74 years to receive either annual screening for 6 years or “usual care” (3). By 2009, 57% of the men had been followed f...

The Catholic Church proscribes methods of birth control other than sexual abstinence. Although the U.S. Food and Drug Administration (FDA) recognizes abstinence as an acceptable method of birth control in research studies, some pharmaceutical companies mandate the use of artificial contraceptive techniques to avoid pregnancy as a condition for part...

Introduction: Alogliptin is a highly selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). It is one of several agents of this class now available for treatment of type 2 diabetes. Areas covered: This review is based upon a PubMed search and personal experience with alogliptin. The pharmacokinetics and pharmacodynamics of alogliptin...

Data-Base Management System (DBMS) is the current standard for storing information. A DBMS organizes and maintains a structure of storage of data. Databases make it possible to store vast amounts of randomly created information and then retrieve items using associative reasoning in search routines. However, design of databases is cumbersome. If one...

Insulin therapy is commonly associated with weight gain. The timing of prandial insulin administration may enhance its efficacy/safety and maintain effective weight control. This study examined the effect of postprandial vs. preprandial insulin glulisine on weight gain and glycaemic control in type 2 diabetes patients taking basal insulin. This was...

SB-509 is a zinc finger DNA-binding protein transcription factor (ZFP-TF) activator that upregulates the expression of vascular endothelial growth factor A (VEGF-A). VEGF-A plays an important role in both angiogenesis and neurological development. Independent research studies show that VEGF-A has direct neurotrophic activity on axonal outgrowth in...

Original article: Taskinen MR, Rosenstock J, Tamminen I, et al. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011;13(1):65-74. PRACTICE PEARL: This trial in patients with type 2 diabetes inadequately controlled on metfor...

Diabetic dermopathy is the most common specific cutaneous finding in diabetes. Using laser Doppler technology, we tested the hypothesis that diabetic dermopathy arises from abnormal local skin blood flow. We measured cutaneous blood flow in patients with type 1 diabetes without dermopathy and compared values with those in a control group of patient...

Clinical research protocols are intricate and detailed. Regulatory authorities including the U.S. Food and Drug Administration require full documentation of all procedures, including who performed them and when they were performed. Paper based study records are becoming ever more voluminous as the requirements for detailing every item continue to g...

We have shown previously that skin perfusion is reduced in patients with diabetes mellitus (DM). Patients with diabetes and with chronic kidney disease (CKD) stage 5 were having advanced microangiopathy. In this cross-sectional study, we measured skin blood flow in DM and non-DM patients on dialysis to assess whether any differences exist in skin p...

To assess the efficacy and safety of alogliptin added to insulin in patients with type 2 diabetes inadequately controlled with insulin alone or combined with metformin. In this 26-week, double-blind, placebo-controlled study, 390 patients were randomized to receive alogliptin 12.5 mg (n = 131), alogliptin 25 mg (n = 129) or placebo (n = 130) once d...

Background Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Inhibition of DPP-4 elevates levels of the incretin hormones glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) by preventing their degradation. Objective To review the evolution of...

Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The pr...

Certain useful pharmaceutical agents carry a high risk of embryopathy. The US Food and Drug Administration (FDA), in cooperation with drug manufacturers, has established pregnancy prevention programs (PPPs) to reduce the incidence of birth defects for thalidomide (STEPS [System for Thalidomide Education and Prescribing Safety]) and isotretinoin (iP...

Carbohydrate counting is an effective approach to mealtime insulin adjustment in type 1 diabetes but has not been rigorously assessed in type 2 diabetes. We sought to compare an insulin-to-carbohydrate ratio with a simple algorithm for adjusting the dose of prandial insulin glusiline. This 24-week, multicenter, randomized, controlled study compared...

Elevated levels of cortisol have been implicated in the development of type 2 diabetes mellitus and the metabolic syndrome. Modulation of cortisol levels and activity may be useful in the treatment of type 2 diabetes and its comorbidities. The purpose of this study was to evaluate the safety profile and pharmacodynamic effects of DIO-902 (2S,4R-ket...

The isolation of insulin by Banting and Best in 1922 was a historic event of life-saving importance. Thousands of individuals doomed to die of type I diabetes were saved. The inspiring story of insulin continued to grow and evolve with the development of PZI, NPH, and lente insulins. The advent of production of human insulin from recombinant DNA br...

With evidence that elevated post-prandial glucose (PPG) is a major risk factor for cardiovascular disease, there is increasing emphasis on primary treatment of PPG in diabetes. The carbohydrate content of a meal is the principal contribution to PPG, so efforts to reduce carbohydrate ingestion are an important dietary approach to management. Althoug...

Necrobiosis lipoidica diabeticorum (NLD) is a granulomatous skin reaction found in < 1% of diabetic patients. Our purpose was to determine if NLD represented areas of cutaneous ischemia. Using laser Doppler flowmetry, we measured cutaneous blood flow in nine diabetic patients at NLD lesions and at contiguous uninvolved sites. Flow values were also...

This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucos...

Over the past 20 years, the treatment armamentarium for diabetes has greatly expanded: 8 different classes of non-insulin drugs and 8 different types of insulin are now available. The newer classes of agents include disaccharidase inhibitors, thiazolidinediones, meglitinides, glucagonlike peptide analogs, and dipeptidyl peptidase IV inhibitors. The...