Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous phenotypes.Due to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and infertility.Furthermore,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general population.Often,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment plan.Historic insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount importance.Sodium-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS armamentarium.Namely,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS.It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

How far along are we in revealing the connection between metformin and colorectal cancer?

Colorectal cancer(CRC)is among the most prevalent cancers worldwide,and its prevention and reduction of incidence is imperative.The presence of diabetes has been associated with a 30%increased risk of CRC,likely through the mechanism of hyperinsulinemia,which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways,inflammation,or adipokines,inducing cancer cell proliferation and cancer spread.Metformin,the first-line agent in treating type 2 diabetes,has a chemopreventive role in CRC development.Additionally,preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon cancer.Although preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy,the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive,and randomized controlled trials are still lacking.

Shifting perspectives-interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals

Non-alcoholic fatty liver disease(NAFLD)has become a significant public health burden affecting not only obese individuals but also people with normal weight.As opposed to previous beliefs,this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese counterparts.The development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype,precisely visceral fat tissue,sarcopenia,and insulin resistance.Here,we summarize available data focusing on the co-dependent relationship between metabolic phenotype,insulin resistance,and development of NAFLD in lean individuals,suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.

Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.