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
Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin ...Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.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
Emphysematous pyelonephritis(EPN)is a severe,a lethal necrotizing upper urinary tract infection,characterized by gas production within the renal pa-renchyma,collecting system,or perinephric tissue.EPN is emerging as a...Emphysematous pyelonephritis(EPN)is a severe,a lethal necrotizing upper urinary tract infection,characterized by gas production within the renal pa-renchyma,collecting system,or perinephric tissue.EPN is emerging as a sig-nificant concern,necessitating early diagnosis,severity assessment,and timely intervention to improve outcomes.This study proposes a modified National Early Warning Score 2(mNEWS 2)to enhance risk stratification and predictive accuracy in EPN management.The mNEWS 2 refines the original NEWS 2 system,which aggregates 6 physiological indicators(body temperature,systolic blood pressure,pulse rate,oxygen saturation,breathing rate,and degree of consciousness),by incorporating weighted risk stratification indices and specific cutoff values derived from clinical observations,statistical modeling,and predictive per-formance analysis.A pilot study identified optimal thresholds,with a score of 15 maximizing predictive performance for mortality risk and intervention needs,validated through receiver operating characteristic curve analysis.So,the mNEWS 2 score represents a significant advancement in EPN management,offering improved risk stratification and treatment outcomes.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
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
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 b...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<sup>®</sup> 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 follow-up 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 long-term 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 and diaphyseal 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
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
This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protectin...This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.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 decline in serum testosterone in ageing men may be mediated in part by obesity; however, it is uncertain which measure of adiposity is most closely associated with testosterone levels. We have examined the relatio...The decline in serum testosterone in ageing men may be mediated in part by obesity; however, it is uncertain which measure of adiposity is most closely associated with testosterone levels. We have examined the relationships of age, adiposity and testosterone levels in ageing men with symptoms consistent with hypoandrogenism but who were otherwise in good health. We conducted a cross-sectional study of non-smoking men aged ≥ 54 years recruited from the community and who were free of cancer or serious medical illness. Height （Ht）, weight and waist circumference （WC） were measured, and body mass index （BMI） and waist-to-height （WHt） ratio were calculated. Two morning blood samples were collected for measurement of total testosterone （TT）, sex hormone binding globulin （SHBG） and luteinizing hormone （LH）. Free testosterone （cFT） was calculated. Multivariate linear regression analysis was performed to assess their relationship with measures of adiposity. Two hundred and seven men aged 54-86 years were studied. On univariate analysis WHt ratio was more strongly correlated with TI＂ and cFT than either WC or BMI. Furthermore, in models of TT and cFT, the addition of Ht to WC resulted in an increase in the magnitude of the regression coefficients for both WC （inverse correlate） and Ht （positive correlate）, with the contributions of both WC and Ht both being significant （P〈0.05 for all）. In conclusion, WHt ratio is the best anthropometric predictor of both TT and cFT in this group of healthy but symptomatic ageing men.展开更多
In men, obesity and metabolic complications are associated with lower serum testosterone （T） and dihydrotestosterone （DHT） and an increased risk of, and mortality from, multiple chronic diseases in addition to car...In men, obesity and metabolic complications are associated with lower serum testosterone （T） and dihydrotestosterone （DHT） and an increased risk of, and mortality from, multiple chronic diseases in addition to cardiovascular disease （CVD）. The causal interrelationships between these factors remain a matter of debate. In men with untreated congenital and lifelong forms of hypogonadotropic hypogonadism, there appears to be no increased risk. Men with Klinefelter＇s syndrome have an increased risk of various types of cancers, as well as CVD, which persist despite T therapy. In the absence of pathology of the hypothalamic-pituitary- gonadal axis, the effect of modest reductions in serum T in aging men is unclear. The prevalence of low serum T concentrations is high in men with cancer, renal disease, and respiratory disease and is likely to be an indicator of severity of systemic disease, not hypogonadism. Some population-based studies have found low serum T to be associated with a higher risk of deaths attributed to cancer, renal disease, and respiratory disease, while others have not. Although a meta-analysis of longitudinal studies has shown an association between low serum T and all-cause mortality, marked heterogeneity between studies limited a firm conclusion. Therefore, while a decrease in T particularly occurring later in life may be associated with an increase in all-cause and specific types of mortality in men, the differential effects, if any, of T and other sex steroids as compared to health and lifestyle factors are unknown at the current time.展开更多
Current treatments for diabetic retinopathy （DR） are based on laser photocoagulation and intravitreal injections of corti- costeroids or anti-vascular endothelial growth factor （VEGF） agents. These treatments are ...Current treatments for diabetic retinopathy （DR） are based on laser photocoagulation and intravitreal injections of corti- costeroids or anti-vascular endothelial growth factor （VEGF） agents. These treatments are applicable only at advanced stages of the disease. In addition, they are expensive, require a vitreo- retinal specialist and are associated with significant adverse ef- fects. Therefore, new pharmacological treatments for the early stages of the disease are needed.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
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
AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 ...AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.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
In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2...In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.展开更多
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Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.
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Emphysematous pyelonephritis(EPN)is a severe,a lethal necrotizing upper urinary tract infection,characterized by gas production within the renal pa-renchyma,collecting system,or perinephric tissue.EPN is emerging as a sig-nificant concern,necessitating early diagnosis,severity assessment,and timely intervention to improve outcomes.This study proposes a modified National Early Warning Score 2(mNEWS 2)to enhance risk stratification and predictive accuracy in EPN management.The mNEWS 2 refines the original NEWS 2 system,which aggregates 6 physiological indicators(body temperature,systolic blood pressure,pulse rate,oxygen saturation,breathing rate,and degree of consciousness),by incorporating weighted risk stratification indices and specific cutoff values derived from clinical observations,statistical modeling,and predictive per-formance analysis.A pilot study identified optimal thresholds,with a score of 15 maximizing predictive performance for mortality risk and intervention needs,validated through receiver operating characteristic curve analysis.So,the mNEWS 2 score represents a significant advancement in EPN management,offering improved risk stratification and treatment outcomes.
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.
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<sup>®</sup> 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 follow-up 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 long-term 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 and diaphyseal 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This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.
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 decline in serum testosterone in ageing men may be mediated in part by obesity; however, it is uncertain which measure of adiposity is most closely associated with testosterone levels. We have examined the relationships of age, adiposity and testosterone levels in ageing men with symptoms consistent with hypoandrogenism but who were otherwise in good health. We conducted a cross-sectional study of non-smoking men aged ≥ 54 years recruited from the community and who were free of cancer or serious medical illness. Height （Ht）, weight and waist circumference （WC） were measured, and body mass index （BMI） and waist-to-height （WHt） ratio were calculated. Two morning blood samples were collected for measurement of total testosterone （TT）, sex hormone binding globulin （SHBG） and luteinizing hormone （LH）. Free testosterone （cFT） was calculated. Multivariate linear regression analysis was performed to assess their relationship with measures of adiposity. Two hundred and seven men aged 54-86 years were studied. On univariate analysis WHt ratio was more strongly correlated with TI＂ and cFT than either WC or BMI. Furthermore, in models of TT and cFT, the addition of Ht to WC resulted in an increase in the magnitude of the regression coefficients for both WC （inverse correlate） and Ht （positive correlate）, with the contributions of both WC and Ht both being significant （P〈0.05 for all）. In conclusion, WHt ratio is the best anthropometric predictor of both TT and cFT in this group of healthy but symptomatic ageing men.
文摘In men, obesity and metabolic complications are associated with lower serum testosterone （T） and dihydrotestosterone （DHT） and an increased risk of, and mortality from, multiple chronic diseases in addition to cardiovascular disease （CVD）. The causal interrelationships between these factors remain a matter of debate. In men with untreated congenital and lifelong forms of hypogonadotropic hypogonadism, there appears to be no increased risk. Men with Klinefelter＇s syndrome have an increased risk of various types of cancers, as well as CVD, which persist despite T therapy. In the absence of pathology of the hypothalamic-pituitary- gonadal axis, the effect of modest reductions in serum T in aging men is unclear. The prevalence of low serum T concentrations is high in men with cancer, renal disease, and respiratory disease and is likely to be an indicator of severity of systemic disease, not hypogonadism. Some population-based studies have found low serum T to be associated with a higher risk of deaths attributed to cancer, renal disease, and respiratory disease, while others have not. Although a meta-analysis of longitudinal studies has shown an association between low serum T and all-cause mortality, marked heterogeneity between studies limited a firm conclusion. Therefore, while a decrease in T particularly occurring later in life may be associated with an increase in all-cause and specific types of mortality in men, the differential effects, if any, of T and other sex steroids as compared to health and lifestyle factors are unknown at the current time.
文摘Current treatments for diabetic retinopathy （DR） are based on laser photocoagulation and intravitreal injections of corti- costeroids or anti-vascular endothelial growth factor （VEGF） agents. These treatments are applicable only at advanced stages of the disease. In addition, they are expensive, require a vitreo- retinal specialist and are associated with significant adverse ef- fects. Therefore, new pharmacological treatments for the early stages of the disease are needed.
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.
基金Supported by National Health and Medical Research Council of AustraliaNHMRC early career fellowship
文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.
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In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.
