Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable blindness.In fact,the American Diabetes Association has defined DR as a highly specif...Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable blindness.In fact,the American Diabetes Association has defined DR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider DR as merely a microvascular complication.In this regard,the term diabetic retinal disease(DRD)has been proposed as a broader term comprising microangiopathy and neurodegeneration.However,there are currently no treatments available that directly target the neurodegenerative changes of DR.This paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase IV(GLP-1/DPP-IV)inhibitors.展开更多
Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monoge...Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.展开更多
Point of care ultrasonography(POCUS)has evolved to become the fifth pillar of the conventional physical examination,and use of POCUS protocols have significantly decreased procedure complications and time to diagnose....Point of care ultrasonography(POCUS)has evolved to become the fifth pillar of the conventional physical examination,and use of POCUS protocols have significantly decreased procedure complications and time to diagnose.However,lack of experience in POCUS by preceptors in medical schools and nephrology residency programs are significant barriers to implement a broader use.In rural and low-income areas POCUS may have a transformative effect on health care management.展开更多
Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level mon...Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.展开更多
Traditional treatment of T2 DM consisting of modification of diet,an exercise regimen,and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time,now bariatric surgery is reco...Traditional treatment of T2 DM consisting of modification of diet,an exercise regimen,and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time,now bariatric surgery is recommended for treatment of obese patients with T2 DM because its great improvements on weight loss and metabolic.In this article,effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.展开更多
Background: Hirsutism is a clinical situation in Cameroon which is poorly elucidated due to a paucity of clinical and biological data;hence our interest in this study. The aim of this work was to describe the clinical...Background: Hirsutism is a clinical situation in Cameroon which is poorly elucidated due to a paucity of clinical and biological data;hence our interest in this study. The aim of this work was to describe the clinical, psycho-social and metabolic profile of women with hirsutism in Yaoundé. Materials and Methods: This was a descriptive cross-sectional study carried out from May 2013 to December 2013. Participants were recruited by announcement through social media. Our study included women at least 18 years old, not in menopausal, not pregnant, not breastfeeding, with hirsutism regardless of severity. They were assessed through an interrogation, anthropometric parameters, a physical examination using the modified Ferriman and Gallwey score, the measurement of fasting capillary blood glucose and a lipid profile. The psycho-social assessment was carried out using a pre-designed questionnaire on the participant’s perception and daily experience with hirsutism. The metabolic syndrome was established according to the criteria of the International Diabetes Federation of 2005 and the National Cholesterol Education Program-third adult treatment panel of 2001. Results: We recruited 60 women aged 27.6 ± 7.0 years. The median Ferriman and Gallwey score was 12. The mean duration of evolution was 9 years. A family history of hirsutism was found in 88.8% of the participants, especially in the mother. Signs of virilization were found in 3.3% of the participants. Association was found between menstrual cycle abnormalities and severity of hirsutism (p = 0.023). Psycho-socially, 58.8% of women found hirsutism normal. The metabolic syndrome was found in 21.7% and 18.3% according to the IDF and NCEP-ATP III, respectively. Conclusion: Hirsutism in our context seems normal to most of our participants. It is, however, associated with menstrual irregularities, signs of virilization and metabolic syndrome. As a result, hirsutism merits further study on a large-scale with emphasis on etiology.展开更多
The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause o...The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide.The cellular and molecular mechanisms of these chronic complications are still poorly understood,preventing the development of effective treatment strategies.Tight junctions(TJs)are epithelial intercellular junctions located at the most apical region of cell-cell contacts,and their main function is to restrict the passage of molecules through the paracellular space.The TJs consist of over 40 proteins,and the most important are occludin,claudins and the zonula occludens.Accumulating evidence suggests that TJ disruption in different organs,such as the brain,nerves,retina and kidneys,plays a fundamental pathophysiological role in the development of chronic complications.Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy,brain injury and diabetic retinopathy.The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown.In the present review,we highlighted the molecular events that lead to barrier dysfunction in diabetes.Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.展开更多
Hydrogen sulfide (H2S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H2S on the development of obesity and the underlying mechanisms, however,...Hydrogen sulfide (H2S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H2S on the development of obesity and the underlying mechanisms, however, have been unclear. Here, we find that a decreased endogenous H2S level lowered lipid accumulation in mouse adipocytes. Exogenous H2S treatment significantly increased the adipogenesis of primary mouse preadipocytes after six days of adipogenic induction. In the early phase of adipogenesis, H2S increased cell proliferation and prepared cells to go through hyperplasia. After H2S treatment for ten days, preadipocytes exhibited significantly greater cell surface area and diameter, indicating cell hypertrophy. Although it stimulated lipid accumulation and adipogenesis, H2S had no effect on lipolysis. With nutrition overload and high glucose/insulin incubation, H2S further stimulated glucose consumption and deteriorated adipocyte hypertrophy. H2S upregulated hyperplasia genes (CCAAT/enhancer-binding protein (C/EBPβ), cell division cycle 25 (Cdc25), minichromosome maintenance 3 (Mcm3), and cell division cycle 45 (Cdc45)) and cyclin-dependent kinase 2 protein (Cdk2), which regulates cell proliferation. H2S also upregulated the insulin receptor β (Irβ)-activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways, leading to adipogenesis. In conclusion, H2S increases adipocyte differentiation, hypertrophy, and hyperplasia, implying that it plays a pathogenic role in obesity disorder.展开更多
Gastric emptying(GE)exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes;the rise in blood glucose following oral carbohydrate is greater when GE is re...Gastric emptying(GE)exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes;the rise in blood glucose following oral carbohydrate is greater when GE is relatively more rapid and more sustained when glucose tolerance is impaired.Conversely,GE is influenced by the acute glycaemic environment acute hyperglycaemia slows,while acute hypoglycaemia accelerates it.Delayed GE(gastroparesis)occurs frequently in diabetes and critical illness.In diabetes,this poses challenges for management,particularly in hospitalised individuals and/or those using insulin.In critical illness it compromises the delivery of nutrition and increases the risk of regurgitation and aspiration with consequent lung dysfunction and ventilator dependence.Substantial advances in knowledge relating to GE,which is now recognised as a major determinant of the magnitude of the rise in blood glucose after a meal in both health and diabetes and,the impact of acute glycaemic environment on the rate of GE have been made and the use of gut-based therapies such as glucagon-like peptide-1 receptor agonists,which may profoundly impact GE,in the management of type 2 diabetes,has become commonplace.This necessitates an increased understanding of the complex inter-relationships of GE with glycaemia,its implications in hospitalised patients and the relevance of dysglycaemia and its management,particularly in critical illness.Current approaches to management of gastroparesis to achieve more personalised diabetes care,relevant to clinical practice,is detailed.Further studies focusing on the interactions of medications affecting GE and the glycaemic environment in hospitalised patients,are required.展开更多
The growing diabetic epidemic has created a substantial burden,not only on the people with diabetes but also on society at large.This mini-review discussed the limitations and patterns of disability in type 2 diabetes...The growing diabetic epidemic has created a substantial burden,not only on the people with diabetes but also on society at large.This mini-review discussed the limitations and patterns of disability in type 2 diabetes mellitus and put forward a case for the moderating effects of physical activity(PA)in the management of diabetes.The limitations and impairments associated with diabetes include vascular,neurological,cardiac,and renal impairments.Moreover,individuals participate less in their daily lives and in their instrumental activities of daily living,which negatively impacts the quality of life of individuals with diabetes.This often leads to a loss of quality of life due to disabilities,resulting in an increased rate of disability-adjusted life years among people with type 2 diabetes mellitus.Moreover,there are psychosocial sequelae of diabetes mellitus.This necessitates looking for moderating factors that may reduce the burden of the disease.PA has been shown to be one of the factors that can mitigate these burdens.PA does this in several ways,including through the benefits it confers,such as a reduction of hemoglobin A1c,a reduction of excess fat in the liver and pancreas,and the reduction of cardiovascular risk factors,all of which favorably affect glycemic parameters.Specifically,PA regulates or moderates diabetes disability through two mechanisms:The regulation of glucolipid metabolism disorders and the optimization of body mass index and systemic conditions.Therefore,efforts should be directed at PA uptake through identified strategies.This will not only prevent diabetes or diabetes complications but will reduce its burden.展开更多
Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal env...Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal environment. The aim of our study was to assess insulin sensitivity in full-term newborns exposed in utero to HIV and ARVs in Yaoundé. Materials and Methods: We conducted an analytical cross-sectional study in 2 maternities in the city of Yaoundé from November 2021 to June 2022. We generated two groups of newborns (NBs): one group born to HIV positive mothers on ARVs and the other control group born to HIV negative mothers. Clinical data from mothers and NBs were collected. A homeostatic model assessment of insulin resistance (HOMA-IR) like index with C peptide served to assess insulin sensitivity. We used the Spearman correlation to measure the strength of association between insulin sensitivity and the different variables. A p-value Results: Of 70 neonates included, 35 were born to HIV positive mothers on ARVs and 35 to HIV negative mothers. The median age of HIV positive and negative mothers was 30 (27 - 32) and 34 (24 - 47) years, respectively (p = 0.791). The body mass index before pregnancy as well as the average newborn weights were comparable in both groups. The ARV protocol associating Tenofovir, Lamivudine, Efavirenz was used by 97.1% of HIV positive mothers. In the exposed NBs group, C peptide was significantly lower (p < 0.001) and blood glucose significantly higher (p < 0.001). The median values of HOMA-IR were 1.4 (0.8 - 1.9) and 2 (1.4 - 2.6) (p = 0.001) for exposed and unexposed NBs, respectively. Conclusion: Newborns exposed to HIV and ARVs had lower C peptide levels and were more sensitive to insulin. Close metabolic monitoring of these newborns would allow early diagnosis and management of any glucose regulation disorder.展开更多
Introduction: The presence of vascular complications at type 2 diabetes (T2D) diagnosis is a heavy burden for developing countries. We aimed to determine the prevalence and correlates of macrovascular complications at...Introduction: The presence of vascular complications at type 2 diabetes (T2D) diagnosis is a heavy burden for developing countries. We aimed to determine the prevalence and correlates of macrovascular complications at T2D diagnosis in Yaoundé, Cameroon. Materials and Methods: We conducted a cross-sectional study at the Essos Hospital Center in Yaoundé from January 2017 to June 2021. We recruited patients newly diagnosed with T2D who, simultaneously, with assessed macrovascular complications including stroke, myocardial infarction (MI) and arterial foot ulcer (AFU). Correlates were investigated using Chi square test and logistic regressions. The significance level was set at 5%. Results: In all, 286 newly diagnosed diabetic patients (51.7% being men) were included. The mean age was 52.6 ± 12.3 years. Prevalent cardiovascular risk factors at diabetes diagnosis were a dyslipidemia (63.6%), sedentary lifestyle (57.7%) and family history of type 2 diabetes (51.6%). The prevalence of macrovascular complications was 17.5% with 8.4% stroke, 5.6% myocardial infarction and 3.4% arterial foot ulcer. Hypertension was associated with all macrovascular complications (p Conclusion: Macrovascular complications are frequent at type 2 diabetes diagnosis and are represented by stroke and myocardial infarction in our study, highlighting the importance of cardiovascular risk evaluation and reduction in people with diabetes right from diagnosis.展开更多
The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however mos...The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.展开更多
Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyper...Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.展开更多
Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal ...Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the cardiovascular system and its protection.展开更多
The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis(UC), paying particular attention to the latest tendency of the research concerning the management of bo...The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis(UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool(FRAX tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a followup only. An intermediate risk supports the decision to prescribe bone mineral density(BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a longterm bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric anddiaphyseal femoral fractures.UC is a long-lasting disease and the majority of patients is relatively young.In this scenario primary prevention of fragility fracture is the best cost-effective strategy.Vitamin D supplementation,adequate calcium intake,suitable physical activity(when possible),removing of risk factors for osteoporosis like smoking,and avoiding falling are the best medical acts.展开更多
Bone remodeling replaces old and damaged bone with new bone through a sequence of cellular events occurring on the same surface without any change in bone shape. It was initially thought that the basic multicellular u...Bone remodeling replaces old and damaged bone with new bone through a sequence of cellular events occurring on the same surface without any change in bone shape. It was initially thought that the basic multicellular unit(BMU) responsible for bone remodeling consists of osteoclasts and osteoblasts functioning through a hierarchical sequence of events organized into distinct stages. However, recent discoveries have indicated that all bone cells participate in BMU formation by interacting both simultaneously and at different differentiation stages with their progenitors, other cells, and bone matrix constituents. Therefore,bone remodeling is currently considered a physiological outcome of continuous cellular operational processes optimized to confer a survival advantage. Bone remodeling defines the primary activities that BMUs need to perform to renew successfully bone structural units. Hence, this review summarizes the current understanding of bone remodeling and future research directions with the aim of providing a clinically relevant biological background with which to identify targets for therapeutic strategies in osteoporosis.展开更多
基金funded by grants from the Instituto de Salud CarlosⅢ(DTS18/0163 and ICI20/00129)co-funded by European Union。
文摘Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable blindness.In fact,the American Diabetes Association has defined DR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider DR as merely a microvascular complication.In this regard,the term diabetic retinal disease(DRD)has been proposed as a broader term comprising microangiopathy and neurodegeneration.However,there are currently no treatments available that directly target the neurodegenerative changes of DR.This paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase IV(GLP-1/DPP-IV)inhibitors.
文摘Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.
文摘Point of care ultrasonography(POCUS)has evolved to become the fifth pillar of the conventional physical examination,and use of POCUS protocols have significantly decreased procedure complications and time to diagnose.However,lack of experience in POCUS by preceptors in medical schools and nephrology residency programs are significant barriers to implement a broader use.In rural and low-income areas POCUS may have a transformative effect on health care management.
文摘Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.
文摘Traditional treatment of T2 DM consisting of modification of diet,an exercise regimen,and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time,now bariatric surgery is recommended for treatment of obese patients with T2 DM because its great improvements on weight loss and metabolic.In this article,effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.
基金supported by the Israel Science Foundation(#786/13)the Fritz Thyssen Stiftung(Germany),and by the Kekst Family Institute for Medical Genetics and the David and Fela Shapell Family Center for Genetic Disorders Research at the Weizmann Institute
文摘肥胖和新陈代谢的症候群和他们的联系病态是主要公共健康问题，谁的流行将继续在可预见的未来增加。为 leptin 和胰岛素的由受体的异常发信号在新陈代谢的症候群的开发起一个枢轴的作用。这两条关键发信号小径怎么被调整的更完全的分子水平的理解为肥胖，新陈代谢的症候群，和类型 II 的完整的描述是必要的糖尿病，并且为为这些疾病开发新奇处理。酷氨酸残余上的蛋白质的 Phosphorylation 在调停起一个关键作用他们的目标房间上的 leptin 和胰岛素的效果。这里，我们讨论蛋白质酷氨酸磷酸酶，是在 vivo 的蛋白质 phosphorylation 的关键生理的管理者，由假装在他们的主要目标纸巾由 leptin 和胰岛素受体发信号的分子的方法。
文摘Background: Hirsutism is a clinical situation in Cameroon which is poorly elucidated due to a paucity of clinical and biological data;hence our interest in this study. The aim of this work was to describe the clinical, psycho-social and metabolic profile of women with hirsutism in Yaoundé. Materials and Methods: This was a descriptive cross-sectional study carried out from May 2013 to December 2013. Participants were recruited by announcement through social media. Our study included women at least 18 years old, not in menopausal, not pregnant, not breastfeeding, with hirsutism regardless of severity. They were assessed through an interrogation, anthropometric parameters, a physical examination using the modified Ferriman and Gallwey score, the measurement of fasting capillary blood glucose and a lipid profile. The psycho-social assessment was carried out using a pre-designed questionnaire on the participant’s perception and daily experience with hirsutism. The metabolic syndrome was established according to the criteria of the International Diabetes Federation of 2005 and the National Cholesterol Education Program-third adult treatment panel of 2001. Results: We recruited 60 women aged 27.6 ± 7.0 years. The median Ferriman and Gallwey score was 12. The mean duration of evolution was 9 years. A family history of hirsutism was found in 88.8% of the participants, especially in the mother. Signs of virilization were found in 3.3% of the participants. Association was found between menstrual cycle abnormalities and severity of hirsutism (p = 0.023). Psycho-socially, 58.8% of women found hirsutism normal. The metabolic syndrome was found in 21.7% and 18.3% according to the IDF and NCEP-ATP III, respectively. Conclusion: Hirsutism in our context seems normal to most of our participants. It is, however, associated with menstrual irregularities, signs of virilization and metabolic syndrome. As a result, hirsutism merits further study on a large-scale with emphasis on etiology.
文摘The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide.The cellular and molecular mechanisms of these chronic complications are still poorly understood,preventing the development of effective treatment strategies.Tight junctions(TJs)are epithelial intercellular junctions located at the most apical region of cell-cell contacts,and their main function is to restrict the passage of molecules through the paracellular space.The TJs consist of over 40 proteins,and the most important are occludin,claudins and the zonula occludens.Accumulating evidence suggests that TJ disruption in different organs,such as the brain,nerves,retina and kidneys,plays a fundamental pathophysiological role in the development of chronic complications.Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy,brain injury and diabetic retinopathy.The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown.In the present review,we highlighted the molecular events that lead to barrier dysfunction in diabetes.Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.
文摘Hydrogen sulfide (H2S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H2S on the development of obesity and the underlying mechanisms, however, have been unclear. Here, we find that a decreased endogenous H2S level lowered lipid accumulation in mouse adipocytes. Exogenous H2S treatment significantly increased the adipogenesis of primary mouse preadipocytes after six days of adipogenic induction. In the early phase of adipogenesis, H2S increased cell proliferation and prepared cells to go through hyperplasia. After H2S treatment for ten days, preadipocytes exhibited significantly greater cell surface area and diameter, indicating cell hypertrophy. Although it stimulated lipid accumulation and adipogenesis, H2S had no effect on lipolysis. With nutrition overload and high glucose/insulin incubation, H2S further stimulated glucose consumption and deteriorated adipocyte hypertrophy. H2S upregulated hyperplasia genes (CCAAT/enhancer-binding protein (C/EBPβ), cell division cycle 25 (Cdc25), minichromosome maintenance 3 (Mcm3), and cell division cycle 45 (Cdc45)) and cyclin-dependent kinase 2 protein (Cdk2), which regulates cell proliferation. H2S also upregulated the insulin receptor β (Irβ)-activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways, leading to adipogenesis. In conclusion, H2S increases adipocyte differentiation, hypertrophy, and hyperplasia, implying that it plays a pathogenic role in obesity disorder.
文摘Gastric emptying(GE)exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes;the rise in blood glucose following oral carbohydrate is greater when GE is relatively more rapid and more sustained when glucose tolerance is impaired.Conversely,GE is influenced by the acute glycaemic environment acute hyperglycaemia slows,while acute hypoglycaemia accelerates it.Delayed GE(gastroparesis)occurs frequently in diabetes and critical illness.In diabetes,this poses challenges for management,particularly in hospitalised individuals and/or those using insulin.In critical illness it compromises the delivery of nutrition and increases the risk of regurgitation and aspiration with consequent lung dysfunction and ventilator dependence.Substantial advances in knowledge relating to GE,which is now recognised as a major determinant of the magnitude of the rise in blood glucose after a meal in both health and diabetes and,the impact of acute glycaemic environment on the rate of GE have been made and the use of gut-based therapies such as glucagon-like peptide-1 receptor agonists,which may profoundly impact GE,in the management of type 2 diabetes,has become commonplace.This necessitates an increased understanding of the complex inter-relationships of GE with glycaemia,its implications in hospitalised patients and the relevance of dysglycaemia and its management,particularly in critical illness.Current approaches to management of gastroparesis to achieve more personalised diabetes care,relevant to clinical practice,is detailed.Further studies focusing on the interactions of medications affecting GE and the glycaemic environment in hospitalised patients,are required.
文摘The growing diabetic epidemic has created a substantial burden,not only on the people with diabetes but also on society at large.This mini-review discussed the limitations and patterns of disability in type 2 diabetes mellitus and put forward a case for the moderating effects of physical activity(PA)in the management of diabetes.The limitations and impairments associated with diabetes include vascular,neurological,cardiac,and renal impairments.Moreover,individuals participate less in their daily lives and in their instrumental activities of daily living,which negatively impacts the quality of life of individuals with diabetes.This often leads to a loss of quality of life due to disabilities,resulting in an increased rate of disability-adjusted life years among people with type 2 diabetes mellitus.Moreover,there are psychosocial sequelae of diabetes mellitus.This necessitates looking for moderating factors that may reduce the burden of the disease.PA has been shown to be one of the factors that can mitigate these burdens.PA does this in several ways,including through the benefits it confers,such as a reduction of hemoglobin A1c,a reduction of excess fat in the liver and pancreas,and the reduction of cardiovascular risk factors,all of which favorably affect glycemic parameters.Specifically,PA regulates or moderates diabetes disability through two mechanisms:The regulation of glucolipid metabolism disorders and the optimization of body mass index and systemic conditions.Therefore,efforts should be directed at PA uptake through identified strategies.This will not only prevent diabetes or diabetes complications but will reduce its burden.
文摘Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal environment. The aim of our study was to assess insulin sensitivity in full-term newborns exposed in utero to HIV and ARVs in Yaoundé. Materials and Methods: We conducted an analytical cross-sectional study in 2 maternities in the city of Yaoundé from November 2021 to June 2022. We generated two groups of newborns (NBs): one group born to HIV positive mothers on ARVs and the other control group born to HIV negative mothers. Clinical data from mothers and NBs were collected. A homeostatic model assessment of insulin resistance (HOMA-IR) like index with C peptide served to assess insulin sensitivity. We used the Spearman correlation to measure the strength of association between insulin sensitivity and the different variables. A p-value Results: Of 70 neonates included, 35 were born to HIV positive mothers on ARVs and 35 to HIV negative mothers. The median age of HIV positive and negative mothers was 30 (27 - 32) and 34 (24 - 47) years, respectively (p = 0.791). The body mass index before pregnancy as well as the average newborn weights were comparable in both groups. The ARV protocol associating Tenofovir, Lamivudine, Efavirenz was used by 97.1% of HIV positive mothers. In the exposed NBs group, C peptide was significantly lower (p < 0.001) and blood glucose significantly higher (p < 0.001). The median values of HOMA-IR were 1.4 (0.8 - 1.9) and 2 (1.4 - 2.6) (p = 0.001) for exposed and unexposed NBs, respectively. Conclusion: Newborns exposed to HIV and ARVs had lower C peptide levels and were more sensitive to insulin. Close metabolic monitoring of these newborns would allow early diagnosis and management of any glucose regulation disorder.
文摘Introduction: The presence of vascular complications at type 2 diabetes (T2D) diagnosis is a heavy burden for developing countries. We aimed to determine the prevalence and correlates of macrovascular complications at T2D diagnosis in Yaoundé, Cameroon. Materials and Methods: We conducted a cross-sectional study at the Essos Hospital Center in Yaoundé from January 2017 to June 2021. We recruited patients newly diagnosed with T2D who, simultaneously, with assessed macrovascular complications including stroke, myocardial infarction (MI) and arterial foot ulcer (AFU). Correlates were investigated using Chi square test and logistic regressions. The significance level was set at 5%. Results: In all, 286 newly diagnosed diabetic patients (51.7% being men) were included. The mean age was 52.6 ± 12.3 years. Prevalent cardiovascular risk factors at diabetes diagnosis were a dyslipidemia (63.6%), sedentary lifestyle (57.7%) and family history of type 2 diabetes (51.6%). The prevalence of macrovascular complications was 17.5% with 8.4% stroke, 5.6% myocardial infarction and 3.4% arterial foot ulcer. Hypertension was associated with all macrovascular complications (p Conclusion: Macrovascular complications are frequent at type 2 diabetes diagnosis and are represented by stroke and myocardial infarction in our study, highlighting the importance of cardiovascular risk evaluation and reduction in people with diabetes right from diagnosis.
文摘The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.
基金Supported by Grants from the Ministerio de Cienciae Innovacion,No.SAF2009-07408CIBER de Diabetesy Enfermedades Metabólicas Asociadas and Generaltitat de Catalunya,No. 2009SGR739
文摘Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.
文摘Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the cardiovascular system and its protection.
文摘The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis(UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool(FRAX tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a followup only. An intermediate risk supports the decision to prescribe bone mineral density(BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a longterm bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric anddiaphyseal femoral fractures.UC is a long-lasting disease and the majority of patients is relatively young.In this scenario primary prevention of fragility fracture is the best cost-effective strategy.Vitamin D supplementation,adequate calcium intake,suitable physical activity(when possible),removing of risk factors for osteoporosis like smoking,and avoiding falling are the best medical acts.
文摘Bone remodeling replaces old and damaged bone with new bone through a sequence of cellular events occurring on the same surface without any change in bone shape. It was initially thought that the basic multicellular unit(BMU) responsible for bone remodeling consists of osteoclasts and osteoblasts functioning through a hierarchical sequence of events organized into distinct stages. However, recent discoveries have indicated that all bone cells participate in BMU formation by interacting both simultaneously and at different differentiation stages with their progenitors, other cells, and bone matrix constituents. Therefore,bone remodeling is currently considered a physiological outcome of continuous cellular operational processes optimized to confer a survival advantage. Bone remodeling defines the primary activities that BMUs need to perform to renew successfully bone structural units. Hence, this review summarizes the current understanding of bone remodeling and future research directions with the aim of providing a clinically relevant biological background with which to identify targets for therapeutic strategies in osteoporosis.
