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Glucagon-like peptide-1(GLP-1) is a multifunctional polypeptide throughout the lifespan via activating Glucagon-like peptide-1 receptor (GLP-1R).GLP-1 can affect food ingestion, enhance the secretion of insulin from pancreatic islets induced by glucose and be utilized to treat type 2 diabetes mellitus(T2DM).But, accumulating evidences from the decades suggest that activation GLP-1R can not only regulate the blood glucose, but also sustain the homeostasis of intracellular environment and protect neuron from various damaged responses such as oxidative stress, inflammation, excitotoxicity, ischemia and so on. And more and more pre-clinical and clinical studies identified that GLP-1 and its analogues may play a significant role in improving multiple central nervous system (CNS) diseases including neurodegenerative diseases, epilepsy, mental disorders, ischemic stroke, hemorrhagic stroke, traumatic brain injury, spinal cord injury, chronic pain, addictive disorders, other diseases neurological complications and so on. In order to better reveal the relationship between GLP-1/GLP-1R axis and the growth, development and survival of neurons, herein, this review is aimed to summarize the multi-function of GLP-1/GLP-1R axis in CNS diseases.

Vitamin D (Vit D) insufficiency is caused basically by inadequately sunlight-induced vitamin D in the skin. It is connected to a variety of ongoing illness, especially diabetes type II. Tests have indicated that Vit D is crucial for glucose-induced insulin production and increased insulin impacts. It diminishes insulin resistance and has anti-inflammatory properties. A few reports showed that the destitute eat less, indicating a negative effect on their wellbeing. Insulin resistance is connected to more Vit D levels. Many RCTs in subjects with type II diabetes recognized slight impacts of Vit D on glycemic and insulin resistance. At the same time, these call for more in-depth investigation and the current study is an excellent avenue to start. There is no reason to prescribe Vit D supplementation to avoid or cure type II diabetes mellitus.

Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

Background Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. Methods Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. Conclusions This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Background: The growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate an understanding of adverse event (AE) reporting in these regions. Objective: The aim of the study was to provide an AE reporting overview in patients using insulin in Africa and the Middle East by characterizing and comparing individual case safety reports (ICSRs) features. Method: The cross-sectional study analyzed ICSR data from a global pharmaceutical company’s pharmacovigilance database for January to December 2018 to describe and compare patient demographics, report sources, reporter types, ICSR seriousness, suspect products, indication for insulin use and AE preferred terms, by country Results: Overall 7076 ICSRs were analyzed, 63.6% from the Middle East. Most ICSRs were nonserious (91.5%), from solicited sources (83.5%), and reported by consumers (70.7%). Patients from the Middle East were, on average, 34.2 years of age, had gestational diabetes mellitus as indication (64.3%), insulin detemir as suspect product (76.5%), and exposure during pregnancy as AE preferred term (89.1%). Patients from Africa were 48.1 years old on average, a higher proportion of type 2 diabetes mellitus was observed (52.2%), human insulin was the suspect product (51.6%), and blood glucose increased the AE preferred term (23.1%). Few macrovascular and microvascular complications were reported (< 1% in both regions). Associations between the region and patient age, gender, report sources, reporter types, indications for insulin use, suspect products, and AE preferred term were significant (p < 0.001). Conclusion: ICSRs features were region-specific and dependent on patient age, gender, report sources, reporter types, suspect products, and AE preferred terms.

Aims To determine the first manifestation of cardiovascular or kidney disease (CVKD) and associated resource use in type 2 diabetes mellitus (T2DM) patients during seven years of follow-up. Methods Observational-retrospective secondary data study using medical records of patients aged ≥18 years with T2DM and without prior CVKD between 2013 and 2019. The index date was 01/01/2013 (fixed date). The manifestation of CVKD was defined by the first diagnosis of heart-failure (HF), chronic-kidney disease (CKD), myocardial-infarction (MI), stroke or peripheral-artery disease (PAD). The main variables were baseline characteristics, manifestation of CVKD, mortality, resource use and costs. Descriptive analyses and Cox model were applied to the data. Results 26,542 patients were selected (mean age: 66.6 years, women: 47.8%, mean duration of T2DM: 17.1 years). 18.7% (N = 4974) developed a first CVKD manifestation during the seven years [distribution: HF (22.4%), CKD (36.6%), MI (14.5%), stroke (15.3%) and PAD (11.3%)]. Overall mortality was 8.3% (N = 2214). The mortality risk of the group that developed HF or CKD as the first manifestation compared to the CVKD-free cohort was higher [HR: 2.5 (95% CI: 1.8–3.4) and 1.8 (95% CI: 1.4–2.3)], respectively. The cumulative costs per patient of HF (€50,942.80) and CKD (€48,979.20) were higher than MI (€47,343.20) and stroke (€47,070.30) and similar to PAD (€51,240.00) vs. €13,098.90 in patients who did not develop CVKD, p Conclusions In T2DM patients, HF and CKD were the first most common manifestations and had higher mortality and re-hospitalisation rates. HF and CKD were associated with the highest resource use and costs for the Spanish National-Health-System.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m2, and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P

In the last five years, the medical community was astonishingly surprised by the sequential large outcome trials that displayed the renal effects of sodium glucose co-transporter inhibitors (SGLT2Is) in type 2 diabetes mellitus (T2DM) patients with or without chronic kidney disease (CKD). This favorable effect was later disclosed in non-diabetic CKD patients. The EMPA-REG OUTCOME trial was the first trial that showed a reduction for the need for dialysis in patients suffering diabetic kidney disease (DKD) by 55%. This figure is double the score achieved by the angiotensin receptor blocker, Losartan, in RENAAL trial. The need for dialysis in DAPA-CKD trial was reduced in diabetic and non-diabetic CKD patients by 33%. The renal-specific composite outcome was reduced by 39% in EMPA-REG trial, 40% in CANVAS study, 47% in DECLARE-TIMI 58 study, 34% in CREDENCE trial, and 44% in DAPA-CKD trial. The greater surprise is the significant favorable effect of SGLT2Is on overall mortality in CKD patients with or without T2DM. Similar survival benefit was not previously encountered with any of the medications used in CKD patients with or without diabetes. In this review, we disclose the results of the DAPA-CKD trial, the CREDENCE trial and those of several cardiovascular outcome trials (CVOT) that used different SGLT2Is and showed that patients with lower eGFR levels may have greater benefit with respect to cardiovascular morbidity than patients with normal kidney function. In addition, we discuss the different mechanisms of action that explain the renal beneficial effects of SGLT2Is.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-diabetic agents that block the reabsorption of glucose in the proximal convoluted tubule of the nephron, thereby contributing to glycosuria and lowering blood glucose levels. SGLT2 inhibitors have been associated with improved cardiovascular outcomes in patients with diabetes, including a reduced risk of cardiovascular death and hospitalizations for heart failure. Recently, DAPA-HF and EMPEROR REDUCED trials showed the beneficial cardiovascular effect of SGLT2 inhibitors in patients with heart failure with consistently reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Moreover, some exploratory studies suggested that these drugs improve Left Ventricular (LV) systolic function and oppose LV adverse remodeling in patients with HFrEF. However, the exact mechanisms that mediated for this benefit are not fully understood. Beyond glycemic control, enhanced natriuresis, increased erythropoiesis, improved endothelial function, changes in myocardial metabolism, anti-inflammatory and anti-oxidative properties may all play an active role in SGLT2 inhibitors' cardiovascular benefits. A deep understanding of the pathophysiological interplay is key to define which HF phenotype could benefit more from SGLT2 inhibitors. Current clinical evidence on the comparison of different HF etiologies is limited to posthoc subgroup analysis of DAPA-HF and EMPEROR-REDUCED, which showed similar outcomes in patients with or without ischemic HF. On the other hand, in earlier studies of patients suffering from diabetes, rates of classic ischemic endpoints, such as myocardial infarction, stroke or coronary revascularization, did not differ between patients treated with SGLT2 inhibitors or placebo. The aim of this review is to discuss whether SGLT2 inhibitors may improve prognosis in patients with ischemic HF, not only in terms of reducing re-hospitalizations and improving left ventricular function but also by limiting coronary artery disease progression and ischemic burden.

Gestational and pregestational diabetes during pregnancy are substantial and growing public health issues. Low-income individuals and individuals who identify as racial and ethnic minorities are disproportionately affected. Food security, which is defined as the degree to which individuals have capacity to access and obtain food, is at the center of nutritional resources and decisions for individuals with diabetes. While increasingly recognized as an important mediator of health disparities in the United States, food insecurity is understudied during pregnancy and specifically among pregnant individuals with diabetes, for whom the impact of food-related resources may be even greater. Previous research has suggested that food insecurity is associated with type 2 diabetes mellitus diagnoses and disease exacerbation in the general adult population. An emerging body of research has suggested that food insecurity during pregnancy is associated with gestational diabetes mellitus diagnoses and adverse diabetes-related outcomes. Additionally, food insecurity during pregnancy may be associated with adverse maternal and neonatal outcomes. Future research and clinical work should aim to further examine these relationships and subsequently develop evidence-based interventions to improve diabetes-related outcomes among pregnant individuals with food insecurity. The purpose of this article is to offer a working definition of food security, briefly review issues of food insecurity and diabetes, summarize research on food insecurity and diabetes-related pregnancy health, and discuss clinical recommendations and areas for future investigation. KEY POINTS: · Research on food insecurity and diabetes-related health is limited.. · The impact of food security on diabetes management and obstetric outcomes is likely significant.. · Future work to evaluate perinatal food security screening is warranted..

A 74-year-old farmer presented to the emergency department (ED) with a 5-day history of left leg pain, swelling and redness. He denied trauma or injury. Background medical history included type 2 diabetes mellitus, diabetic neuropathy, right lower limb lymphoedema, recurrent left leg and foot

A 49-year-old woman with a medical history of type 2 diabetes mellitus, hypertension, obstructive sleep apnoea and morbid obesity presented to the pulmonary clinic with chest discomfort on her right side. On physical examination, the patient was in no acute distress, had air entry bilaterally with

Type 2 diabetes mellitus (T2DM) is a progressive meta-inflammatory disorder, which induce micro and macrovascular complications. Resveratrol is a nutraceutical known to have antioxidant and anti-inflammatory properties. It improves insulin resistance; however, no clear evidence regarding its effects in patients with T2DM.We aimed to evaluate the efficacy and the safety of oral resveratrol supplementation in type 2 diabetic patients concerning dose and duration.We searched PubMed, Cochrane Library, Scopus, WOS, Wiley, and Google Scholar for RCTs evaluating the efficacy and safety of resveratrol on patients with T2DM. We screened the studies for the eligibility criteria, performed the quality assessment, extracted the studies' characteristics, baseline, and outcome data of interest, and finally conducted the meta-analysis using RevManV5.3.This systematic review and meta-analysis, including 17 RCTs with total 871 patients with T2DM, showed that resveratrol was superior to placebo on fasting blood glucose (FBG) and total cholesterol (TC) with doses ≥500mg {MD=-13.34, 95%CI [-22.73, -3.95], P=0.005}, {MD=-5.64, 95%CI [-6.95, -4.33], P0.00001} respectively. Moreover, it improved HbA1c at three months {MD=-0.41, 95%CI [-0.65, -0.16], P=0.001 and systolic blood pressure {MD: -7.91, 95%CI [-10.44, -5.37], P0.00001}.We concluded that resveratrol beneficially modulates glycemic control as well as cardiometabolic parameters in patients with T2DM.

Vitamin D is known to affect the functions of pancreatic beta cells, but the effects of vitamin D deficiency on glucoregulatory mechanisms are still inconclusive. The aim of this study was to link vitamin D levels with parameters of insulin resistance and insulin secretion. The study included 70 male and female participants, 40 newly diagnosed patients with type 2 diabetes mellitus (T2DM) and 30 healthy controls. All participants were tested for fasting glucose, hemoglobin A1c, fasting insulin, vitamin D levels, and the HOMA indexes were calculated using HOMA2 calculator. Fasting glucose levels, insulinemia, hemoglobin A1c levels and HOMA IR were all significantly higher in the diabetic group (p

Background/aims We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study. Methods Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m2), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis. Results Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85). Conclusions MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

Aim: Dapagliflozin improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) and is approved in European and Japanese patients with type 1 diabetes mellitus (T1DM) with inadequate glycaemic control. The objectives of this work were to characterise the dapagliflozin pharmacokinetics (PK) in patients with T1DM, assess the influence of covariates on dapagliflozin PK, and compare dapagliflozin systemic exposure between patients with T1DM and T2DM. Methods: Population PK analysis was performed using a non-linear mixed-effect modelling approach. The analysis included 5,793 dapagliflozin plasma concentrations from 1,150 adult patients with T1DM, collected from one phase 2 (NCT01498185) and two phase 3 studies (DEPICT-1, NCT02268214; DEPICT-2, NCT02460978). Covariate effects were investigated using stepwise covariate modelling. Model-derived area under the concentration-time curve (AUC) was compared with AUC in patients with T2DM. Results: The final two-compartmental model adequately described the dapagliflozin concentrations in patients with T1DM. The estimated apparent clearance was 20.5 L/h. Model-predicted systemic exposure for 5 mg and 10 mg of dapagliflozin indicated dose-proportionality and was comparable between patients with T1DM and T2DM. The identified covariate relationships showed that patients with better renal function (measured as estimated glomerular filtration rate), males, and heavier patients had lower dapagliflozin systemic exposure. Among the covariates studied, no covariates affected dapagliflozin systemic exposure to a clinically relevant extent. Conclusions: Dapagliflozin PK in patients with T1DM was adequately described by the population PK model and no clinically relevant covariates were identified. Dapagliflozin systemic exposure was comparable between patients with T1DM and T2DM. NCT01498185, NCT02268214, NCT02460978

Resumen La diabetes mellitus tipo 2 (DMT2) es una enfermedad caracterizada por un estado inflamatorio cronico en la que algunos marcadores como las concentraciones de lipidos se han encontrado frecuentemente alterados. Se han descrito otros marcadores de inflamacion alterados como las interleucinas 6, 8 y el factor de necrosis tumoral, sin embargo, existe poca informacion acerca del comportamiento del indice neutrofilo/linfocito (INL), la relacion plaquetas/linfocitos (RPL) y el indice monocitos/linfocitos (IML), los coeficientes lipidicos y el indice aterogenico en pacientes con DMT2. Objetivo Describir los parametros aterogenicos y de inflamacion en un grupo de pacientes con DMT2. Materiales y metodos Se incluyeron y analizaron los antecedentes clinicos (antecedentes de la enfermedad, comorbilidad, tabaquismo y otras variables relevantes), asi como parametros hematologicos, bioquimicos y antropometricos de 42 pacientes, y se calcularon y evaluaron los coeficientes aterogenicos e indices de inflamacion. Resultados Se encontraron concentraciones elevadas de citocinas proinflamatorias IL-6 e IL-8, factor de necrosis tumoral-α y elevado INL. El 88% de los pacientes fueron clasificados como de alto riesgo de acuerdo con el indice aterogenico. Los pacientes exfumadores exhibieron niveles menores de IL-8 y niveles mas altos de INL comparados con los que nunca han fumado. Conclusion La evaluacion de marcadores aterogenicos y de inflamacion tales como el indice aterogenico, IL-8 y la INL permiten identificar a un subgrupo de pacientes con un alto riesgo de complicaciones graves y mortalidad.

Introduction Diabetes mellitus (DM) is included in the disease group described as the pandemic of the century. Although disease management is possible, it can significantly reduce the quality of life when glycaemic control is poor. The objective of this systematic review was to examine the effectiveness of different educational programmes on the management of the disease among type 2 DM patients. Methods In the literature review, the flow chart of PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) was used. A literature search was conducted from 2010 to 2020 using the Ulakbim National Database, Google Scholar, Scopus, PubMed, Library, Science Direct, Web of Science, Medline, Ebscohost and Cochrane Library, and 18 English randomised controlled studies were included. Results Within the scope of these studies, it was found that individualised and face-to-face training and long-term follow-up after the training were effective on metabolic control. Peer support was also determined as an important factor in the efficacy of the training. In line with the training, the self-management and quality-of-life scores of the individuals with diabetes were positively affected. Conclusions It can be suggested that planned and regular training has a positive effect on metabolic control variables, self-management behaviours and quality of life of individuals with diabetes. Regular training for individuals with diabetes and follow-up for more than 6 months are recommended since they have a positive effect on the disease. It is also recommended to integrate peer support into training programmes.

Background. The safety and efficacy of combination tablets of metformin plus sulfonylurea or plus dipeptidyl peptidase-4 inhibitors have not been studied previously. This study aimed to compare the efficacy and safety of Gliconorm versus Sitavia plus among patients with type 2 diabetes mellitus who fast Ramadan. Methods. This was an open-label study conducted from 1 May 2018 till 1 July 2018. People with type 2 diabetes mellitus who were drug-naive or on metformin only, with HbA1c < 10 % were included. The participants were divided into two groups. The first group was given Gliconorm (glibenclamide 5 mg + metformin 1000 mg), while the second group was given Sitavia plus (sitagliptin 50 mg + metformin 1000 mg) imme-diately after Iftar. Glycated hemoglobin (HbA1c) was measured before and after Ramadan. Several home recordings of blood glucose were collected. In addition, patients were asked to report any hypoglycemic or severe hyperglycemic episodes. Results. A total of 34 participants (18 women) (19 in the first group and 15 in the second group) were involved the study. The mean age was 49.6 ± 9.3 years. HbA1c reduced from 8.7 % (72 mmol/mol) to 7.6 % (60 mmol/mol) and from 8.7% (72 mmol/mol) to 7.7 % (61 mmol/mol) in the first and second group, respectively (p < 0.0001). Only one patient in the first group experienced one episode of hypoglycemia and hyperglycemia. Conclusion. Both medications seem to be safe and effective during Ramadan fasting.

Background The number of people diagnosed with dementia worldwide is set to increase significantly. While patients with dementia often have comorbidities, particularly diabetes, patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study aimed to determine whether older people with T2DM exhibit specificity in cognitive function. Methods The Montreal Cognitive Assessment (MoCA) is a well-known tool for examining mild cognitive impairment. The modified Japanese version (MoCA-J) has been confirmed as effective. We conducted an investigative survey to assess the cognitive function of Japanese individuals aged ≥75 years with and without T2DM, using the MoCA-J, and analyzed the results. Results Thirty-three patients with T2DM and 23 non-DM patients completed the examination. Between both groups, a significant difference in the MoCA-J total scores was found. (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM showed scores ≥26, which is the cutoff point for mild cognitive impairment, whereas all patients had the ability of self-care. Additionally, older patients with T2DM had significantly lower delayed recall scores than the non-DM group. Conclusions Patients aged ≥75 years with T2DM might have lower cognition than those without T2DM; the inability to perform delayed recall in T2DM patients might denote a cognitive function decline.Therefore, compared with other patients, patients aged ≥75 years with T2DM need to receive individually tailored explanations about their care, based on their cognition.

Background: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. Methods: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the 2 nd test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. Results: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. Conclusions: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk for severe coronavirus disease 2019 (COVID-19) and related mortality. Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have significant cardiovascular and renal benefits for patients with T2DM and related comorbidities. Their anti-inflammatory properties could be beneficial in these patients. This work provides less-biased estimates regarding the risk for respiratory tract infections and acute respiratory distress syndrome by performing the first significant meta-analysis of cardiovascular outcome trials in the literature. Notably, GLP-1-RAs do not seem to increase the risk for respiratory tract infection, pneumonia, or acute respiratory distress syndrome in patients with T2DM and cardiovascular comorbidities.

Reducing the risk of death due to cardiovascular disease (CVD) is an important direction for diabetes prevention and treatment. The Chinese population with type 2 diabetes (T2D) has a high risk of developing CVD at relatively low body mass index (BMI) levels. Currently, no studies have evaluated the effect of bariatric surgery versus medical therapy on long-term CVD risk in patients with T2D and low BMI.To compare bariatric surgery versus medical therapy for long-term CVD risk in Chinese patients with T2D and low BMI by using the China Prediction for ASCVD Risk equations and the United Kingdom Prospective Diabetes Study risk engine.University hospital, China.Medical records of patients with T2D with a BMI35 kg/mA total of 684 patients with T2D underwent bariatric surgery (n = 75) or medical therapy (n = 609), and 52 pairs of matched subjects were selected from both groups after propensity score matching. The 10-year and lifetime atherosclerotic CVD risk by using the China Prediction for ASCVD Risk equation at 5 years follow-up period in the bariatric surgery group improved significantly compared with the medical therapy group. In the fifth year of follow-up, the 10-year risk of coronary heart disease, fatal coronary heart disease, stroke, and fatal stroke by using the United Kingdom Prospective Diabetes Study risk engine were much lower in the bariatric surgery group than in the medical therapy group (10.37 ± 5.64% versus 27.25 ± 7.28%, P = .004; 6.3 ± 4.5% versus 22.3 ± 7.35%, P = .002; 4.97 ± 3.73% versus 15.05 ± 3.63%, P = .001; .59 ± .45% versus 1.52 ± .14%, P.001. respectively). The use of glucose-lowering medications, including insulin, was reduced from baseline in both groups, and patients in the bariatric surgery group required significantly fewer of these medications than those in the medical therapy group.Bariatric surgery in patients with T2D and low BMI conferred a lower calculated risk of CVD compared with medical therapy over 5 years of follow-up.

Background: Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.Methods: We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.Results: As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).Conclusion: Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

Background: Despite the importance of and social concern regarding prevention of diabetes at younger ages, limited data are available. This study sought to analyze changes in the prevalence of type 2 diabetes mellitus (T2DM) in Koreans younger than 30 years according to sex, age, and level of income.Methods: The dataset analyzed in this study was derived from health insurance claims recorded in the National Health Insurance Service (NHIS) database. Participants’ level of income was categorized as low (quintile 1

BACKGROUND: According to the World Health Organization, one in ten adults will have Type 2 Diabetes Mellitus (T2DM) in the next few years. Autonomic dysfunction is one of the significant complications of T2DM. Autonomic dysfunction is usually assessed by standard Ewing’s test and resting Heart Rate Variability (HRV) indices. OBJECTIVE: Resting HRV has limited use in screening due to its large intra and inter-individual variations. Therefore, a combined approach of resting and orthostatic challenge HRV measurement with a machine learning technique was used in the present study. METHODS: A total of 213 subjects of both genders between 20 to 70 years of age participated in this study from March 2018 to December 2019 at Smt. Kashibai Navale Medical College and General Hospital (SKNMCGH) in Pune, India. The volunteers were categorized according to their glycemic status as control (n= 51 Euglycemic) and T2DM (n= 162). The short-term ECG signal in the resting and after an orthostatic challenge was recorded. The HRV indices were extracted from the ECG signal as per HRV-Taskforce guidelines. RESULTS: We observed a significant difference in time, frequency, and non-linear resting HRV indices between the control and T2DM groups. A blunted autonomic response to an orthostatic challenge quantified by percentage difference was observed in T2DM compared to the control group. HRV patterns during rest and the orthostatic challenge were extracted by various machine learning algorithms. The Classification and Regression Tree (CART) model has shown better performance among all the machine learning algorithms. It has shown an accuracy of 84.04%, the sensitivity of 89.51%, a specificity of 66.67%, with an Area Under Receiver Operating Characteristic Curve (AUC) of 0.78 compared to resting HRV alone with 75.12% accuracy, 86.42% sensitivity, 39.22% specificity, with an AUC of 0.63 for differentiating autonomic dysfunction in non-diabetic control and T2DM. CONCLUSION: It was possible to develop a Classification and Regression Tree (CART) model to detect autonomic dysfunction. The technique of percentage difference between resting and orthostatic challenge HRV indicates the blunted autonomic response. The developed CART model can differentiate the autonomic dysfunction using both resting and orthostatic challenge HRV data compared to only resting HRV data in T2DM. Thus, monitoring HRV parameters using the CART model during rest and after orthostatic challenge may be a better alternative to detect autonomic dysfunction in T2DM as against only resting HRV.

Introduction: Diabetes mellitus is a heterogeneous group of diseases, characterized by chronic hyperglycemia, resulting from environmental and genetic causes. Aim - To study the cases of type 2 diabetes mellitus attending urban health training centre of community medicine department of tertiary care hospital, Maharashtra. Method: It was a hospital based observational descriptive study done in urban health training centre from January to December 2016 including all known cases of type 2 diabetes mellitus which was around 700. Result: Maximum cases were from age group 40-49 years (38.16 %) and 48% were males and 52 % were females. Maximum cases were Hindu 43% having unskilled occupation 19% and nuclear family 46%. Whereas 37% and 18 % study subjects were having BMI of 25- 29.9 and and ≥ 30 respectively, 28 % were having family history of diabetes mellitus, 37% were having Hypertension, 55 % men and 57% women were having abnormal waist-hip ratio, 29 % men and 09 % women were having habit of alcohol intake. Whereas 37% men and 25% women were having habit of tobacco intake. Conclusion: Type 2 diabetes mellitus patients having modifiable and non-modifiable risk factors for the causation of the disease.

The prevalence of obesity is a major cause of many chronic metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. Insulin resistance is often associated with metabolic unhealthy obesity (MUO). Therapeutic approaches aiming to improve insulin sensitivity are believed to be central for the prevention and treatment of MUO. However, current antiobesity drugs are reported as multitargeted and their insulin-sensitizing effects remain unclear. In this review, we discuss current understanding of the mechanisms of insulin resistance from the aspects of endocrine disturbance, inflammation, oxidative, and endoplasmic reticulum stress (ERS). We then summarize the antiobesity drugs, focusing on their effects on insulin sensitivity. Finally, we discuss strategies for obesity treatment.

Background Increasingly, studies have addressed the possible association between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA), although this remains an issue of controversy. Our aim in this study was to investigate the association between T2DM and OA among 7781 adults ≥50 years of age, through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2011 through 2018. Methods Amultivariable logistic regression model was used to evaluate the association between T2DM or prediabetes status and OA, with subgroup analyses performed, stratified by age, sex, body mass index (BMI), and race. Results Of the 7781 participants enrolled, 1567 (20.1%) had T2DM, 3131 (40.3%) had prediabetes, and 3083 (39.6%) were normal. A significant positive association was identified between T2DM and OA, after adjusting for age, sex, and race. This association, however, was no longer significant after adjusting for BMI. In the fully-adjusted model, there were no significant association between T2DM and OA. Conclusions Our findings showed no association between T2DM and OA. The association between T2DM and OA can be strongly confounded by BMI.

This study aims to explore the effect of mobile phone-based telemedicine management of glycemic control of type 2 diabetes mellitus (T2DM).Patients with T2DM were followed up in Chongqing Jiulongpo District Yuzhoulu Community Health Center, and randomly divided into the telemedicine group (n=47) and the control group (n=50). The control group received regularly routine intervention. The telemedicine management group used the mobile phone to manage their health condition remotely.Both groups had similar baseline characteristics. After a follow-up period of 12 months intervention, the weight, body mass index, waist circumference, systolic blood pressure, body fat percentage, body fat mass, body water and muscle mass, fasting blood glucose, glycosylated hemoglobin, total costs of diabetes treatment for 1 month and the quality-of-life score were significantly improved in the telemedicine group (P0.05). And compared with the control group, body fat composition, fasting blood glucose, glycosylated hemoglobin and the cost of change shows a significant improvement (P0.05). Positive correlation was detected between fasting blood glucose and body composition parameters, such as body fat percentage, lean body mass and body fat mass in the telemedicine group (r=0.56, P0.05; r=0.37, P0.05; r=0.56, P0.05).Compared with conventional intervention, the mobile phone-based telemedicine management can help patients with T2DM to improve glycemic level and quality of life.

OBJECTIVES Private managed healthcare organizations in South Africa (SA) use a capitation model of care for patients within their healthcare delivery systems for the optimal management of type 2 diabetes mellitus (T2DM) to reduce healthcare costs. Few studies have categorized healthcare costs at a patient level to determine the actual healthcare costs incurred by private insurers for T2DM in SA. This study estimated the direct medical costs of patients with T2DM registered with a private health insurer over a 5-year period between 2 funding models: a capitated risk-sharing model (CM) versus a traditional fee-for-service (FFS) model. METHODS This population-based cohort study used retrospective claims data of patients with T2DM from 2012 to 2016 of a private medical scheme in SA. Annual healthcare costs of T2DM were assessed. RESULTS During the 5-year period, most of the identified patients with T2DM were enrolled in CM-534 (64%) of 828 in 2012, which rose to 789 (81%) of 971 in 2016. The median annual healthcare costs of the treatment and management of the patients with T2DM was significantly higher in CM ($2002 [interquartile range (IQR) 2106] in 2012 to $1095 [IQR 1042] in 2016) than FFS ($582 [IQR 772] to $296 [IQR 507]) (P

Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage kidney disease (ESKD) worldwide [1]. The development of chronic kidney disease (CKD) in patients with T2DM substantially increases their risk for cardiovascular (CV) morbidity and mortality [2]. In fact, when T2DM and early-stage CKD co-exist, the risk for CV death is several times higher than the risk for progression to ESKD [3]. Therefore, there is a need for the development of novel therapies to improve CV and kidney failure outcomes in this high-risk population. In this brief perspective, we explore the role of sodium-glucose co-transporter type-2 (SGLT-2) inhibitors and the nonsteroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, in the management of diabetic kidney disease (DKD).

Type 2 Diabetes Mellitus (T2DM) is one of major life style disorder with multiple systemic complications. Lifestyle modification and management of chronic mental stress plays a major role in treating and preventing T2DM. Naturopathy uses lifestyle modification and natural therapies to cure the diseases. Effectiveness of Yoga practice in stress management is proven through various studies. In this study we evaluate the effect of Naturopathy and Yogic lifestyle intervention on the anthropometric, biochemical, electrophysiological parameters and development of cardiovascular risk among T2DM patients. Methods The study is a prospective randomized parallel group trial. The study is divided into two phases, intensive phase and continuation phase. 252 T2DM patients will be randomized into intervention group and control group after screening. The intervention group will receive intense NY CTRI/2018/12/016550

A 79-year-old woman with type 2 diabetes receiving insulin was rushed to our hospital due to severe hypoglycemia. Glucose was administered, and the consciousness disturbance was promptly improved. A few hours later, conjugate deviation of the eyes to the right and left hemiplegia occurred at a normal glucose level. Cerebral magnetic resonance imaging showed hyperintensities of the right posterior limb of the internal capsule and the medial thalamus on diffusion-weighted imaging sequences. However, the changes observed using magnetic resonance imaging disappeared completely on the third day, and her symptoms subsequently improved. This may have been a case of glucose reperfusion injury.

OBJECTIVES: The aims of this study are to (1) create clusters of joint temporal patterns of diet and physical activity (PA), and (2) determine the association of these clusters with health status indicators including body mass index (BMI), waist circumference (WC), fasting plasma glucose, hemoglobin A1c, triglyceride, high-density lipoprotein cholesterol, total cholesterol, blood pressure and health outcomes including obesity, Type 2 Diabetes (T2DM) and metabolic syndrome (MS) in U.S. adults 20–65 years. METHODS: A random day of PA from accelerometry data and the first day 24 hour dietary recall collected in the National Health and Nutrition Examination Survey 2003–2006 were used to determine absolute PA intensity, absolute energy intake, and the time of these activities. Dietary and PA data from 1,627 U.S. adults were Z-normalized. Dynamic time warping (DTW) coupled with kernel-k means clustering algorithm was used to develop joint temporal dietary and PA patterns that maximally partition individuals with similar temporal behaviors into mutually exclusive clusters derived from the data rather than predefined standards. Multivariate regression models adjusted for ptential confounders, multiple comparisons and survey design factors determined associations between joint temporal patterns and health status indicators along with health outcomes (P

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are a class of oral antihyperglycemic drugs recently added to clinical practice guidelines to manage type 2 diabetes mellitus (T2DM). Recent clinical trials have established significant benefits in using SGLT-2is to treat both heart failure and renal disease. This article aims to explain the clinical benefits of inhibiting sodium-glucose cotransporter-2 proteins in patients with T2DM, renal disease, and heart failure. These authors also seek to guide nurse practitioners in prescribing SGLT-2is. Evidence-based guidance for nurse practitioners to treat T2DM, heart failure, and renal disease is likely to improve patients’ clinical outcomes and decrease associated morbidities.

Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon-like peptide 1 (GLP-1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP-1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti-addiction treatment. Studies in rodents and non-human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP-1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

Hyperglycemia often occurs after the transition from intravenous insulin infusion (IVII) to subcutaneous insulin. Weight-based basal insulin initiated earlier in the course of IVII in the medical intensive care unit (MICU), and a weight-based basal-bolus regimen after IVII, can potentially improve post-IVII glycemic control by 48 hours.This prospective study included 69 patients in MICU who were on IVII for ≥24 hours. Exclusions were end-stage renal disease, type 1 diabetes mellitus, and the active use of vasopressors. The intervention group received weight-based basal insulin (0.2-0.25 units/kg) with IVII and weight-based bolus insulin after IVII. The control group received current care. The primary end points were glucose levels at specific time intervals up to 48 hours after IVII.There were 25 patients in the intervention group and 44 in the control group. The mean age of the patients was 59 ± 15 years, 32 (47%) were men, and 52 (78%) had prior diabetes mellitus. The 2 groups were not different (acute kidney injury/chronic kidney disease, pre-existing diabetes mellitus, illness severity, or nothing by mouth status after IVII), except for the steroid use, which was higher in the control group than in the intervention group (34% vs 12%, respectively). Glucose levels were not lower until 36 to 48 hours after IVII (166.8 ± 39.1 mg/dL vs 220.0 ± 82.9 mg/dL, P.001). When controlling for body mass index, nutritional status, hemoglobin A1C, and steroid use, glucose level was lower starting at 12 to 24 hours out (166.87 mg/dL vs 207.50 mg/dL, P = .015). The frequency of hypoglycemia was similar between the 2 groups (5.0% vs 7.1%). The study did not reach target enrollment.The addition of weight-based basal insulin during, and basal-bolus insulin immediately after, IVII in MICU results in better glycemic control at 24 hours after IVII with no increased hypoglycemia.

Background: The rs7932837 polymorphism in the Hematopoietically expressed homeobox (HHEX) gene was discovered through genome-wide association studies and is a promising candidate for type 2 diabetes mellitus (T2DM), which is one of the risk factors for obesity and other complications. T2DM has been identified as a heterogeneous and multifactorial disease characterized by insulin resistance and secretion. Aim: The aim of this study was to investigate the rs7932837 polymorphism in the HHEX gene in overweight patients diagnosed with T2DM in the Saudi Population. Methods: In this case-control study, one hundred T2DM cases and 100 controls were selected based on inclusion and exclusion criteria. Genotyping was performed with polymerase chair reaction-restriction fragment length polymorphism analysis and statistical analysis was performed between T2DM cases and controls for clinical characteristics, genotype and allele frequencies and multiple logistic regression analysis. Results: In this study, T2DM cases were compared with healthy control subjects. Clinical characteristic analysis revealed the statistical analysis between age, weight, BMI, FBG, HDL-c, TC, TG and family history (p

Aims Diabetes can significantly impact quality of life and mental health. However, inconsistencies have been reported in the prevalence of depression in those with Type 1 and Type 2 diabetes, and those without. Systematic reviews also included studies without adequate control subjects. We update existing literature, by comparing depression prevalence between individuals with and without Type 1 and Type 2 diabetes. Methods A systematic review and meta-analysis. We searched MEDLINE, EMBASE and PSYCHINFO, from January 1985 to August 2021. Studies were excluded if they failed to have an adequate control group, specified type of diabetes, or reported depression prevalence by type of diabetes. Results 44 studies were selected for inclusion. The prevalence of depression was significantly higher in people with Type 1 (22% vs 13%, OR = 2.10 (95% CI: 1.23, 3.52)), or Type 2 diabetes (19% vs 11%, OR = 1.76 (1.55, 2.01)) compared to those without diabetes. There was no association between study effect size and mean age or gender. Findings did not significantly differ between methods of depression assessment. Prevalence of depression in people with diabetes was higher in studies carried out in specialist care (36%, OR = 3.14 (2.12, 4.63)) compared to those in community or primary care (12%, OR = 1.51 (1.35, 1.70) and in low- and middle-income countries (OR = 2.58 (1.91, 3.50) compared to countries with high income economies (OR = 1.59 (1.39, 1.82)). Conclusions Depression prevalence remains significant in those with type 1 and type 2 diabetes. Effective chronic disease management in people with diabetes is important, particularly screening and managing depression and diabetes distress in specialist care settings.

Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts. Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable- adjusted regression and were replicated in the independent UK Biobank. Results: The Dallas Heart Study included 2064 participants (mean SD age, 449 years; 54% female; 47% black). High VATehigh LF and high VATelow LF were associated with prevalent atheroscle- rosis, whereas low VATehigh LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VATehigh LF and high VATelow LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VATehigh LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N1⁄422,354; April 2014-May 2020), only high VATelow LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]). Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual. Funding: National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK106520]; National Center for Advancing Translational Sciences [UL1TR001105]; Swedish Research Council [VR-2019-04751]

Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer’s disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; NCI/NNC=934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z5=2.15, p=0.03; I2=98.08%), C-reactive protein (CRP; NCI/NNC=1610/4363, SMD 0.80 [0.50, 1.11], Z14=5.25, p

his study was conducted to examine the effect of telephone counseling based on the Information, Motivation, Behavioral Skills (IMB) Model on HbA1c and self-management in patients with type 2 diabetes mellitus (T2DM). Methods: This study was conducted between January 2019 and September 2019 with a total of 63 (31 interventions, 32 controls) T2DM patients. The intervention group was followed-up for a total of 12 weeks, after 45−60 min of patient training based on IMB, a weekly reminder message and a phone call every two weeks. No intervention was made to the control group. Data were collected at the beginning of the study and at the end of the 12th week. The data were obtained using a Patient Information Form, the Type 2 Diabetes Self-Efficacy Scale, the Diabetes Self-Management Questionnaire (DSMQ), the Perceived Diabetes Self Management Scale (PDSMS) and glycemic control (HbA1c). Results: Participants were on average 54 years old and the majority were female (58.1%). According to the results of the covariance analysis (ANCOVA), there was a statistically significant difference between the pre-post-test HbA1c (F:13.589; p < 0.001), weight (F:32.176; p < 0.001) and systolic blood pressure (F:7.109; p = 0.01). However, there was no significant difference in diastolic blood pressure between the intervention and control groups (F:2.686; p = 0.106). Also, after three months of follow-up, self-efficacy (F:26.632; p < 0.001), self-management (F:44.487; p < 0.001) and self-management perceptions (F:71.132; p < 0.001) were significantly higher in the intervention group. Conclusion: The researchers concluded that telephone counseling based on the IMB model could be a suitable method to improve glycemic control and self-care behaviors in patients with type 2 diabetes.

Objective Type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus. Methods Medline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness. Results A total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): −6.02%, confidence interval (CI): −10.37% to −1.67%] and SGLT2 inhibitors (MD: −2.60%, CI: −4.87% to −0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: −0.06, CI: −0.10 to −0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein. Conclusion Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.

Dapagliflozin is an inhibitor of human renal sodium-glucose cotransporter 2 (SGLT2), first approved for the treatment of type 2 diabetes mellitus (T2DM). Dapagliflozin is primarily metabolized by uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). The effect of UGT1A9 polymorphisms on dapagliflozin apparent oral clearance (CL/F) was studied with dapagliflozin population pharmacokinetic data and UGT1A9 genotype data (I.399CT, rs2011404, rs6759892, rs7577677, rs4148323, UGT1A9*2 and UGT1A9*3) from a Phase 2 study conducted in subjects with T2DM (n = 187). An analysis of covariance (ANCOVA) model accounting for known covariates influencing dapagliflozin CL/F was applied to these data to quantify the impact of each UGT1A9 polymorphism relative to the wildtype UGT1A9 genotype. The analysis showed that the geometric mean ratios of dapagliflozin CL/F for all of the UGT1A9 polymorphisms studied were within the range of wildtype UGT1A9 CL/F values. Consequently, the polymorphisms of UGT1A9 studied had no clinically meaningful impact on the CL/F of dapagliflozin.

Останніми роками спостерігається зростання інте-ресу до метаболічних змін при остеоартриті. В оглядовій статті підсумовані дані щодо метаболічного фенотипу остеоартриту, ролі ожиріння, дисліпідемії, цукрового діабету в розвитку метаболічного фенотипу. Поточні проспективні епідеміологічні дослідження демонструють наявність чітких асоціацій між остеоартритом і компонентами метаболічного синдрому. Деякі дослідники схильні розглядати метаболічний остеоартрит тільки як наслідок надлишкового навантаження на опорні суглоби внаслідок ожиріння. Однак численні недавні дослідження продемонстрували, що адипокіни і цитокіни, що продукуються жировою тканиною, гіперглікемія, інсулінорезистентність та дисліпідемія здатні порушувати метаболізм суглобових тканин. Вісцеральне ожиріння, дисліпідемія й інсулінорезистентність формують особливий вид запалення — низькорівневе, хронічне, пов’язане з метаболічними розладами, що отримало назву «метазапалення». Саме цей вид запалення відіграє вирішальну роль в патогенезі ожиріння, цукрового діабету 2-го типу та його ускладнень, а множинні сигнальні шляхи пов’язують інсулінорезистентність та імунну відповідь. Ожиріння здійснює двояку дію на перебіг остеоартриту: механічний вплив на опорні суглоби, а також генерація метазапалення, що порушує метаболізм суглобових тканин неопірних суглобів. Таким чином, ожиріння може впливати на патогенез і прогресування остеоартриту за допомогою біомеханічних ефектів, а також при збільшенні метастимулюючого запалення.

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.