The physiology of endocrine systems with ageing.
The lancet. Diabetes & endocrinology
During ageing, the secretory patterns of the hormones produced by the hypothalamic-pituitary axis change, as does the sensitivity of the axis to negative feedback by end hormones. Additionally, glucose homoeostasis tends towards disequilibrium with increasing age. Along with these endocrine alterations, a loss of bone and muscle mass and strength occurs, coupled with an increase in fat mass. In addition, ageing-induced effects are difficult to disentangle from the influence of other factors that are common in older people, such as chronic diseases, inflammation, and low nutritional status, all of which can also affect endocrine systems. Traditionally, the decrease in hormone activity during the ageing process has been considered to be detrimental because of the related decline in bodily functions. The concept of hormone replacement therapy was suggested as a therapeutic intervention to stop or reverse this decline. However, clearly some of these changes are a beneficial adaptation to ageing, whereas hormonal intervention often causes important adverse effects. In this paper, we discuss the effects of age on the different hypothalamic-pituitary-hormonal organ axes, as well as age-related changes in calcium and bone metabolism and glucose homoeostasis.
10.1016/S2213-8587(18)30026-3
Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.
The Lancet. Child & adolescent health
Unexplained or idiopathic pituitary stalk thickening or central diabetes insipidus not only harbours rare occult malignancies in 40% of cases but can also reflect benign congenital defects. Between 2014 and 2019, a multidisciplinary, expert national guideline development group in the UK systematically developed a management flowchart and clinical practice guideline to inform specialist care and improve outcomes in children and young people (aged <19 years) with idiopathic pituitary stalk thickening, central diabetes insipidus, or both. All such cases of idiopathic pituitary stalk thickening and central diabetes insipidus require dynamic pituitary function testing, specialist pituitary imaging, measurement of serum β-human chorionic gonadotropin and alpha-fetoprotein concentrations, chest x-ray, abdominal ultrasonography, optometry, and skeletal survey for occult disease. Stalk thickening of 4 mm or more at the optic chiasm, 3 mm or more at pituitary insertion, or both, is potentially pathological, particularly if an endocrinopathy or visual impairment coexists. In this guideline, we define the role of surveillance, cerebrospinal fluid tumour markers, whole-body imaging, indications, timing and risks of stalk biopsy, and criteria for discharge. We encourage a registry of outcomes to validate the systematic approach described in this guideline and research to establish typical paediatric stalk sizes and the possible role of novel biomarkers, imaging techniques, or both, in diagnosis.
10.1016/S2352-4642(21)00088-2
Nonpharmacological Management of Diabetic Foot Ulcers: An Update.
Eleftheriadou Ioanna,Samakidou Georgia,Tentolouris Anastasios,Papanas Nikolaos,Tentolouris Nikolaos
The international journal of lower extremity wounds
Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus that is associated with increased morbidity and mortality, as well as substantial economic burden for the health care system. The standard of care for DFUs includes pressure off-loading, sharp debridement, and wound moisture balance, along with infection control and management of peripheral arterial disease. A variety of advanced modalities that target distinct pathophysiological aspects of impaired wound healing in diabetes are being studied as possible adjunct therapies for difficult to heal ulcers. These modalities include growth factors, stem cells, cultured fibroblasts and keratinocytes, bioengineered skin substitutes, acellular bioproducts, human amniotic membranes, oxygen therapy, negative pressure wound therapy, and energy therapies. Additionally, the use of advanced biomaterials and gene delivery systems is being investigated as a method of effective delivery of substances to the wound bed. In the present narrative review, we outline the latest advances in the nonpharmacological management of DFUs and summarize the efficacy of various standard and advanced treatment modalities.
10.1177/1534734620963561
The potential of transdermal nitric oxide treatment for diabetic peripheral neuropathy and diabetic foot ulcers.
Walton David M,Minton Stephen D,Cook Alonzo D
Diabetes & metabolic syndrome
The Center for Disease Control (CDC) estimates that 29 million Americans have diabetes, and 70% of diabetic patients develop diabetic peripheral neuropathy [1,2]. Up to 27% of the direct medical cost of diabetes may be attributed to DPN [3]. A 2013 article from the American Diabetes Association reported a $176 billion direct medical cost of diabetes in 2012 [4]. DPN patients often suffer from shooting and burning pain in their distal limbs and a severe loss of sensation. Diabetic foot ulcers, infections, and amputations may follow. Currently available treatments: tricyclic antidepressants, anticonvulsants such as gabapentin and pregabalin, serotonin and norepinephrine reuptake inhibitor, duloxetine, topical 5% lidocaine (applied to the most painful area) can manage painful symptoms but do not address the underlying pathologies of DPN and diabetic wound ulcers. A combination of pain-reducing medications can provide relief when individual medications fail, and opioids such as tramadol and oxycodone may be administered with these medications to reduce pain [5]. Due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. Our hypothesis is that a deficiency of nitric oxide synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes DPN; and this could be treated with vasodilators such as nitric oxide. In this paper, the mechanisms of DPN are reviewed and analyzed to elucidate the potential of a transdermal nitric oxide application for the treatment of DPN and diabetic wound ulcers by increasing vasodilation.
10.1016/j.dsx.2018.07.003
Traditional Medicine and Type 2 Diabetes in First Nations Patients.
Canadian journal of diabetes
BACKGROUND:Diabetes may be a cultural experience for many First Nations patients. In this study, we explore the potential role for traditional medicine in the treatment of diabetes. METHODS:A responsive interviewing qualitative methodology was used for 10 First Nations key informant interviews. The first objective was to accurately "re-tell" participants' stories. The second was to develop an overview of traditional medicine and its role in health and diabetes management by synthesizing academic literature, pre-existing local knowledge and perspectives, and stories shared by elders and traditional healers. The traditional medicine healers gave specific permission for this study and its publication. RESULTS:There is a strong cultural and historic context for the experience of diabetes in First Nations. Political and cultural suppression, lifestyle change and ongoing social determinants of health place diabetes in a unique context and generate a sense of fatalism. Traditional medicine can facilitate individual empowerment by connecting a patient with the lessons of previous generations and traditional beliefs and practices. CONCLUSIONS:Traditional medicine can be a valuable resource for First Nations patients living with diabetes and should be considered as a therapeutic modality.
10.1016/j.jcjd.2021.05.007
The impact of chemical engineering and technological advances on managing diabetes: present and future concepts.
Szunerits Sabine,Melinte Sorin,Barras Alexandre,Pagneux Quentin,Voronova Anna,Abderrahmani Amar,Boukherroub Rabah
Chemical Society reviews
Monitoring blood glucose levels for diabetic patients is critical to achieve tight glycaemic control. As none of the current antidiabetic treatments restore lost functional β-cell mass in diabetic patients, insulin injections and the use of insulin pumps are most widely used in the management of glycaemia. The use of advanced and intelligent chemical engineering, together with the incorporation of micro- and nanotechnological-based processes have lately revolutionized diabetic management. The start of this concept goes back to 1974 with the description of an electrode that repeatedly measures the level of blood glucose and triggers insulin release from an infusion pump to enter the blood stream from a small reservoir upon need. Next to the insulin pumps, other drug delivery routes, including nasal, transdermal and buccal, are currently investigated. These processes necessitate competences from chemists, engineers-alike and innovative views of pharmacologists and diabetologists. Engineered micro and nanostructures hold a unique potential when it comes to drug delivery applications required for the treatment of diabetic patients. As the technical aspects of chemistry, biology and informatics on medicine are expanding fast, time has come to step back and to evaluate the impact of technology-driven chemistry on diabetics and how the bridges from research laboratories to market products are established. In this review, the large variety of therapeutic approaches proposed in the last five years for diabetic patients are discussed in an applied context. A survey of the state of the art of closed-loop insulin delivery strategies in response to blood glucose level fluctuation is provided together with insights into the emerging key technologies for diagnosis and drug development. Chemical engineering strategies centered on preserving and regenerating functional pancreatic β-cell mass are evoked in addition as they represent a permanent solution for diabetic patients.
10.1039/c9cs00886a
Recent advances of nanomedicine-based strategies in diabetes and complications management: Diagnostics, monitoring, and therapeutics.
Wang Yanan,Wang Chunhui,Li Keyang,Song Xinyu,Yan Xuefeng,Yu Liangmin,He Zhiyu
Journal of controlled release : official journal of the Controlled Release Society
Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia driven by insulin deficiency or resistance, imposing a significant global burden affecting 463 million people worldwide in 2019. This review has comprehensively summarized the application of nanomedicine with accurate, patient-friendly, real-time properties in the field of diabetes diagnosis and monitoring, and emphatically discussed the unique potential of various nanomedicine carriers (e.g., polymeric nanoparticles, liposomes, micelles, microparticles, microneedles, etc.) in the management of diabetes and complications. Novel delivery systems have been developed with improved pharmacokinetics and pharmacodynamics, excellent drug biodistribution, biocompatibility, and therapeutic efficacy, long-term action safety, as well as the improved production methods. Furthermore, the effective nanomedicine for the treatment of several major diabetic complications with significantly improved life qualities of diabetic patients were discussed in detail. Going through the literature review, several critical issues of the nanomedicine-based strategies applications need to be addressed such as stabilities and long-term safety effects in vivo, the deficiency of standard for formulation administration, feasibility of scale-up, etc. Overall, the review provides an insight into the design, advantages and limitations of novel nanomedicine application in the diagnostics, monitoring, and therapeutics of DM.
10.1016/j.jconrel.2021.01.002
Mechanism of action of yoga on prevention and management of type 2 diabetes mellitus: Narrative review.
Journal of bodywork and movement therapies
BACKGROUND:Research in India has recognized Type 2 Diabetes Mellitus (t2dm) and prediabetes (pdm) as psychosomatic metabolic endocrine disorders characterized by glycemic disharmony. This review aimed at collating information from published e-papers on mechanism of action (MOA) of yoga therapy(YT) and integrated approach of yoga therapy (IAYT) on pdm and t2dm. METHOD:Content on YT and the MOA on prevention and management of t2dm were extracted from online sources such as PubMed, Google Scholar, Cochrane library and Library genesis. This review included 58 articles related to prediabetes, t2dm, pre-diabetes to t2dm conversion, mechanism of action of Yoga, Yoga and t2dm, prediabetes and yoga. Articles related to type 1 diabetes, diabetes insipidus and gestational diabetes were excluded. RESULT:Current scientific review resulted in understanding the different mechanisms involved in rejuvenating effect of Yoga as YT and IAYT in prediabetes and t2dm. However, the various mechanisms by which the interventions work are understood either through a single or combined impact on regaining autonomic balance, vagal modulation, regulation of hormones and thereby attaining glycemic control. Moreover, these mechanisms are the forthcomings of the cross talk between brain, mind and body systems under branches of neurophysiology, neuroendocrinology, psychophysiology, psycho neuroendocrinology and/or neuropsychology. CONCLUSION:Evidence sought from published research works proclaim YT based life style modification for prevention and management of t2dm. Summing up, the effect is stipulated based on the approach, method of practice, time of the day, belief and dedication of the practitioners.
10.1016/j.jbmt.2021.10.003
Emerging Theranostic Nanomaterials in Diabetes and Its Complications.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Diabetes mellitus (DM) refers to a group of metabolic disorders that are characterized by hyperglycemia. Oral subcutaneously administered antidiabetic drugs such as insulin, glipalamide, and metformin can temporarily balance blood sugar levels, however, long-term administration of these therapies is associated with undesirable side effects on the kidney and liver. In addition, due to overproduction of reactive oxygen species and hyperglycemia-induced macrovascular system damage, diabetics have an increased risk of complications. Fortunately, recent advances in nanomaterials have provided new opportunities for diabetes therapy and diagnosis. This review provides a panoramic overview of the current nanomaterials for the detection of diabetic biomarkers and diabetes treatment. Apart from diabetic sensing mechanisms and antidiabetic activities, the applications of these bioengineered nanoparticles for preventing several diabetic complications are elucidated. This review provides an overall perspective in this field, including current challenges and future trends, which may be helpful in informing the development of novel nanomaterials with new functions and properties for diabetes diagnosis and therapy.
10.1002/advs.202102466
Corneal endothelial cell density during diabetes mellitus and ocular diabetes complications treatment.
Pont C,Ascaso F J,Grzybowski A,Huerva V
Journal francais d'ophtalmologie
Diabetes mellitus may affect the cornea at various levels. Ocular surface changes and dry eye had been studied. Researchers are concerned that medical treatment of diabetes or retinal complications may result in endothelial damage and cell loss. This report summarizes the possibility of endothelial cell loss in diabetic patients. A decrease in endothelial cell density (ECD) in diabetic patients has been reported. In addition, corneal thickness may increase in diabetic patients. Significant endothelial cell loss has been demonstrated in long-term disease and in cases of poor metabolic control. No association between the use of oral hypoglycemics and ECD has been reported. There is also no evidence of an association between the use of insulin and corneal endothelial damage. No difference in ECD among the various degrees of retinopathy or with a history of photocoagulation has been shown. Regarding the studies comparing diabetic and non-diabetic patients undergoing cataract surgery, in all cases, the decrease in ECD is higher in diabetic patients than that seen in non-diabetic patients. However, there is no evidence of increased endothelial damage in diabetics compared to non-diabetics during vitreo-retinal surgery in phakic eyes. No significant changes in corneal endothelium after intravitreal anti-VEGF injections have been referenced.
10.1016/j.jfo.2019.12.003
Current Approaches in Diabetes Treatment and Other Strategies to Reach Normoglycemia.
Sirhan Worood,Piran Ron
Current topics in medicinal chemistry
Cells are mainly dependent on glucose as their energy source. Multicellular organisms need to adequately control individual glucose uptake by the cells, and the insulin-glucagon endocrine system serves as the key glucose regulation mechanism. Insulin allows for effective glucose entry into the cells when blood glucose levels are high, and glucagon acts as its opponent, balancing low blood glucose levels. A lack of insulin will prevent glucose entry to the cells, resulting in glucose accumulation in the bloodstream. Diabetes is a disease which is characterized by elevated blood glucose levels. All diabetes types are characterized by an inefficient insulin signaling mechanism. This could be the result of insufficient insulin secretion, as in the case of type I diabetes and progressive incidents of type II diabetes or due to insufficient response to insulin (known as insulin resistance). We emphasize here, that Diabetes is actually a disease of starved tissues, unable to absorb glucose (and other nutrients), and not a disease of high glucose levels. Indeed, diabetic patients, prior to insulin discovery, suffered from glucose malabsorption. In this mini-review, we will define diabetes, discuss the current status of diabetes treatments, review the current knowledge of the different hormones that participate in glucose homeostasis and the employment of different modulators of these hormones. As this issue deals with peptide therapeutics, special attention will be given to synthetic peptide analogs, peptide agonists as well as antagonists.
10.2174/1568026620666200716113813
GENETICS IN ENDOCRINOLOGY Pathophysiology, diagnosis and treatment of familial nephrogenic diabetes insipidus.
Bichet Daniel G
European journal of endocrinology
For an endocrinologist, nephrogenic diabetes insipidus (NDI) is an end-organ disease, that is the antidiuretic hormone, arginine-vasopressin (AVP) is normally produced but not recognized by the kidney with an inability to concentrate urine despite elevated plasma concentrations of AVP. Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. For a geneticist, hereditary NDI is a rare disease with a prevalence of five per million males secondary to loss of function of the vasopressin V2 receptor, an X-linked gene, or loss of function of the water channel AQP2. These are small genes, easily sequenced, with a number of both recurrent and private mutations described as disease causing. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter's syndrome and cystinosis. MAGED2 mutations are responsible for a transient form of Bartter's syndrome with severe polyhydramnios. The purpose of this review is to describe classical phenotype findings that will help physicians to identify early, before dehydration episodes with hypernatremia, patients with familial NDI. A number of patients are still diagnosed late with repeated dehydration episodes and large dilations of the urinary tract leading to a flow obstructive nephropathy with progressive deterioration of glomerular function. Families with ancestral X-linked AVPR2 mutations could be reconstructed and all female heterozygote patients identified with subsequent perinatal genetic testing to recognize affected males within 2 weeks of birth. Prevention of dehydration episodes is of critical importance in early life and beyond and decreasing solute intake will diminish total urine output.
10.1530/EJE-20-0114
Precision medicine in diabetes: a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
Diabetologia
The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as 'diabetes'. Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment) and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e. monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realise its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
10.1007/s00125-020-05181-w
Diabetes or endocrinopathy admitted in the COVID-19 ward.
European journal of clinical investigation
The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.
10.1111/eci.13262
Management of diabetes mellitus in dialysis patients: Obstacles and challenges.
Alalawi Fakhriya,Bashier Alaaeldin
Diabetes & metabolic syndrome
BACKGROUND AND AIMS:Diabetic kidney disease (DKD) is a major health issue that is associated with an increased risk of morbidity and mortality. The treatment of DKD is challenging given changes in blood glucose homeostasis, unclear accuracy of glucose metrics, and altered kinetics of the blood glucose-lowering medications. There is uncertainty surrounding the optimal glycemic target in this population although recent epidemiologic data suggest that HbA1c ranges of 6-8%, as well as 7-9%, are associated with increased survival rates among diabetic dialysis patients. Furthermore, the treatment of diabetes in patients maintained on dialysis is challenging, and many blood glucose-lowering medications are renally metabolized and excreted hence requiring dose adjustment or avoidance in dialysis patients. METHOD:ology: PubMed, Google Scholar, and Medline were searched for all literature discussing the management of diabetes in dialysis patients. RESULTS:The literature was discussed under many subheadings providing the latest evidence in the treatment of diabetes in dialysis patients. CONCLUSION:The management of diabetes in dialysis is very complex requiring a multi-disciplinary team involving endocrinologists and nephrologists to achieve targets and reduce morbidity and mortality.
10.1016/j.dsx.2021.05.007