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Alzheimer's disease (AD) is closely related to type 2 diabetes (T2D). This study investigated the impact of high-intensity interval training (HIIT) on diabetes-induced disturbances in AD-related factors (including AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), and tau protein) in the hippocampus, with the main focus on adiponectin signaling.In total, 28 male Wistar rats at the age of 8 weeks were randomly assigned to four groups (n = 7 in each group): control (Con), type 2 diabetes (T2D), HIIT (Ex), and type 2 diabetes + HIIT (T2D + Ex). T2D was induced by a high-fat diet plus a single dose of streptozotocin (STZ). Rats in Ex and T2D + Ex groups performed 8 weeks of HIIT (running at 8-95% of V max , 4-10 intervals). Insulin and adiponectin levels in serum and hippocampus were measured along with hippocampal expression of insulin and adiponectin receptors, phosphorylated AMPK, dephosphorylated GSK3β, and phosphorylated tau. Homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for insulin resistance beta (HOMA-β), and quantitative insulin sensitivity check index (QUICKI) were calculated to assess insulin resistance and sensitivity. T2D decreased insulin and adiponectin levels in serum and hippocampus, as well as the hippocampal levels of insulin and adiponectin receptors and AMPK, but increased GSK3β and tau in the hippocampus. HIIT reversed diabetes-induced impairments and consequently decreased tau accumulation in the hippocampus of diabetic rats. HOMA-IR, HOMA-β, and QUICKI were improved in Ex and T2D + Ex groups. Overall, our results confirmed that T2D has undesirable effects on the levels of some Alzheimer's-related factors in the hippocampus, and HIIT could ameliorate these impairments in the hippocampus., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is conflicting evidence on the effect of vitamin D on glycemic control. Therefore, in the current meta-analyses, we aimed to assess the effect of vitamin D supplementation on the glycemic control of type 2 diabetes (T2D) patients., Methods: We conducted a comprehensive search in electronic databases including; PubMed/Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and NIH's Clinical Trials Registry, from the inception of each database up to January first, 2021., Results: A total of 46 randomized controlled trials (RCTs) consisting of 2164 intervention subjects and 2149 placebo controls were included in this meta-analysis. Pooled analyses for HbA1c showed a significant change between the intervention and placebo group, the weighted mean difference (WMD)(95% confidence interval(CI)) was -0.20%(-0.29, -0.11) with P < 0.001. Analyses for assessing changes in FPG found a significant reduction in the intervention group after vitamin D supplementation, the WMD (95%CI) was -5.02 mg/dl (-6.75,-3.28) with P < 0.001. The result of pooled analyses for HOMA-IR revealed a significant change between the intervention and control group, the WMD (95%CI) was -0.42(-0.76, -0.07) with P = 0.019. The subgroup analyses showed the most efficacy in a higher dose and short intervention period and in subjects with deficient vitamin D status., Conclusion: Vitamin D supplementation might be beneficial for the reduction of FPG, HbA1c, and HOMA-IR in type 2 diabetes patients with deficient vitamin D status. This effect was especially prominent when vitamin D was given in large doses and for a short period of time albeit with substantial heterogeneity between studies and a probability of publication bias., (© 2023. The Author(s).)

Aim: To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D)., Methods: We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed., Results: We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] μIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D., Conclusions: Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes., Methods: A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed., Results: The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01-3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05-1.18, p < 0.001); however they could not predict the severity of retinopathy. In ROC analysis AUC for TNFα was 0.849 (p < 0.001) and for NO was 0.907 (p < 0.001). Serum TNF-α level of 7.10 pmol/L could be suggestive of the presence of retinopathy (sensitivity = 92.2% and specificity = 66.0%), also serum NO level of 45.96 μmol/L could be suggestive of the presence of retinopathy (sensitivity = 96.1% and specificity = 86%)., Conclusions: Our results suggest elevated levels of NO and TNF-α can be suggestive of diabetic retinopathy.

Background: Bariatric surgery is an effective treatment for obesity and its associated comorbidities. This is the first comprehensive report of a prospective cohort study, comparing sleeve gastrectomy (SG) with gastric bypass (GB) regarding their effectiveness and safety., Methods: The prospectively collected data of patients, who presented to a specialized bariatric center and underwent a primary bariatric procedure, were compared in terms of weight loss, remission of obesity-associated comorbidities, complication rate, and quality of life improvement at 6-, 12-, and 24-month follow-ups., Results: Of 3287 patients (78.6% female) analyzed, 67% (n = 2202) and 33% (n = 1085) underwent SG and GB, respectively. Effective outcomes were reported in both groups regarding the body composition indices. Type 2 diabetes mellitus (T2DM) remission rate at the end of follow-up was 53.3% and 63.8% in the SG and GB groups, respectively. Following the propensity score-adjusted analysis, the T2DM remission rate was not significantly different between the groups. Conversely, the remission rate of hypertension in the 24-month follow-up (39.1% vs. 54.7%) and the remission rate of dyslipidemia in all follow-ups were lower in the SG group, compared to the GB group. Moreover, both procedures caused substantial improvements in various domains of quality of life. The surgery duration, early complication rate, and nutritional deficiencies were lower in the SG group, compared to the GB group., Conclusion: Both surgical procedures were effective in the control of obesity and remission of its comorbidities. However, since SG was associated with a lower rate of complications, it seems that SG should be considered as a suitable procedure for obese patients, especially those with a healthier metabolic profile.

Type 2 diabetes mellitus (T2DM) is a growing global health concern. The pathogenesis of T2DM is multifactorial and intricate, involving a complex interplay of genetic predisposition, environmental factors, and molecular interactions. Vitamin D (circulating 25-hydroxyvitamin D concentration) regulates factors crucial for T2DM, including insulin secretion, sensitivity, and inflammation. Thus, vitamin D deficiency has been linked to poor health outcomes in T2DM patients. The cholesterol-synthesizing enzyme 7-dehydrocholesterol reductase (DHCR7) represents a critical regulatory switch between cholesterol and vitamin D3 synthesis. Recent findings suggest that the enzyme DHCR7 may indicate T2DM glycolipid metabolic disorder and is associated with deficient circulating vitamin D (circulating 25-hydroxyvitamin D concentration) status. In this PRISMA-guided systematic review, articles were sourced from two databases, namely, PubMed and Cochrane Library, to evaluate the impact of vitamin D deficiency in patients with T2DM and to explore the emerging role of DHCR7 in T2DM pathogenesis. Our findings strongly indicate a positive correlation between deficient vitamin D status and poor health outcomes in T2DM patients. Finally, this systematic review presents a novel perspective on T2DM development, focusing on the interplay between T2DM-associated hyperglycemia, expression of DHCR7, and abrogation of vitamin D synthesis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Scope: Patients with Type 2 diabetes mellitus (T2DM) have lower levels of vitamin D. An elevation in uric acid (UA) contributes to T2DM via an increase in oxidative stress. Adenosine deaminase (ADA) is an enzyme of the purine degradation pathway. It is hypothesized that a reduction of ADA activity via vitamin D supplementation reduces UA and oxidative stress., Methods and Results: A total of 162 participants (81 with T2DM and 81 controls) are enrolled in a case-control study. A follow-up interventional study is performed on 30 patients with vitamin D deficiency. These patients receive 50 000 IU (international units) of vitamin D3 on a weekly basis for 12 weeks. This intervention is followed by the measurement of several markers. T2DM patients has higher ADA activity, UA, and lipid peroxidation but lower 25-hydroxy-vitamin D (25 (OH) vitamin D) and GSH/GSSG ratio (p < 0.05). Vitamin D supplementation results in a reduction of ADA activity and UA levels (p < 0.05) along with an increase in GSH/GSSG ratio (p < 0.05)., Conclusion: The results highlight the presence of an axis in T2DM patients between ADA, UA, and oxidative stress. Modulation of this axis can be achieved by clinically approved vitamin D supplementation protocols., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Objective: It has been reported that early menarche is associated with higher risk for type 2 diabetes. We aimed to explore the association between age at menarche and risk of type 2 diabetes in a population-based cohort study., Methods: For the purpose of the present study, 5191 subjects of reproductive age who were participants of the Tehran Lipid and Glucose Study and also met the eligibility criteria were selected. Demographic, lifestyle, reproductive, and anthropometric data as well as risk factors for metabolic diseases were collected. Menarcheal age was categorized into five categories, as <11 years, 11-12 years, 13-14 years, 15-16 years, and >17 years. Diabetes and pre-diabetes were defined according to the American Diabetes Association criteria. Logistic regression analysis was used to assess the risk of the menarcheal age group for type 2 diabetes and pre-diabetes., Results: Of 5625 participants, 673 women had pre-diabetes and 187 had diabetes. Early menarche was associated with higher risk of diabetes and pre-diabetes, compared to the reference group (13-14 years), (OR=3.55, 95% CI: 1.6-7.8 and OR=2.55, 95% CI:1.4-4.8, respectively), an association which remained after further adjustment for potential confounders including family history of diabetes, parity, education, age, body mass index, waist circumference, smoking history, physical activity, and duration of oral contraceptives use., Conclusion: Results showed early menarche to be a potential risk factor for type 2 diabetes and pre-diabetes.

Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF)., Methods and Results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m 2 and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus ≥60 ml/min/1.73 m 2 , from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus ≥6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively., Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient subgroups and discontinuations., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life., Methods: In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05., Results: A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models., Conclusion: Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Aims: Emerging evidence suggests that platelet count predicts the development of type 2 diabetes; however, there is conflicting evidence concerning the relationship in men and women. This study aimed to assess the longitudinal association between platelet count and the incidence risk of type 2 diabetes., Materials and Methods: Among 10,030 participants, 7325 participants (3439 men and 3886 women) without diabetes were selected from the Korean Genome and Epidemiology Study. Platelet count quartiles were divided as follows: Q1 ≤219, Q2, 220-254, Q3, 255-296 and Q4 ≥297 (x10 3 /ml) for men and ≤232, 233-266, 267-305 and ≥306 (x10 3 /μL) for women. The hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes were calculated using multiple Cox proportional hazards regression models according to sex-specific platelet count quartiles., Results: During the biennial follow-up period from 2001 to 2002 to 2013-2014, 750 male participants (21.8%, 750/3439) and 730 female participants (18.8%, 730/3886) had newly developed type 2 diabetes. For women, compared to the reference first quartile, the HRs for incident type 2 diabetes in the second, third, and fourth platelet count quartiles were 1.20 (0.96-1.50), 1.21(0.97-1.51), and 1.47 (1.18-1.82) after adjusting for age, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and HOMA-IR. However, these positive relationships were not observed in men after adjusting for the same co-variables., Conclusions: Platelet count was independently associated with an increased risk of incident type 2 diabetes only in women., (© 2023 John Wiley & Sons Ltd.)

Purpose: Diabetes mellitus has long been widely considered to be associated with an increased risk of urinary tract infection (UTI), but information on incidence rates are scarce and risk factor data have been conflicting. The aim was to estimate UTI incidence and evaluate potential risk factors for UTI in patients with type 2 diabetes included in recent clinical trials., Methods: Type 2 diabetes patients from 10 AstraZeneca phase III diabetes clinical trials (n=6016, mean 57.4 years, 50.7% female) conducted during 2004-2007 were included. Patients free of UTI at baseline were followed for up to 6 months after inclusion in the trials. UTI was considered present if any term sorting under the MedDRA high-level term "UTIs" was recorded as an adverse event., Results: In all, 142 patients had an adverse event for UTI, corresponding to an incidence of 59.5/1000 person-years for all patients (91.5/1000 in women, 28.2/1000 in men) and a cumulative incidence of 2% during 6 months. Female gender was associated with an increased incidence [relative risk (RR) 3.4; 95% confidence interval (CI) 2.3-5.1] and also higher age (RR 2.5 [95% CI 1.4-4.8] for ages ≥ 70 years vs. 40-49 years). No increased incidence was associated with body mass index (25-29, 30+ vs. <25 kg/m(2) ), HbA1c (<8% vs. >8%), race (Black, Oriental vs. Caucasian) or drug treatment (study drug, comparator vs. placebo). A history of immune system disorder conveyed a twofold higher risk for UTI., Conclusion: UTI is common among female patients with type 2 diabetes and older patients of both genders., (Copyright © 2010 John Wiley & Sons, Ltd.)

Objective: Menopausal hormone therapy (MHT) is known to reduce the incidence of type 2 diabetes mellitus (T2DM); however, since the Women's Health Initiative study, the types and doses of female hormones used for MHT have changed considerably. Therefore, this study was conducted to determine whether MHT, which is currently widely prescribed, increases the risk of T2DM., Method: We performed a retrospective cohort study based on national health insurance data and cancer screening data from 2002 to 2019. We included the MHT group as postmenopausal women older than 40 years who used at least one MHT for at least 6 months between 2003 and 2011. We subclassified the MHT group into five categories; tibolone, combined estrogen plus progestin by the manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by the physician (CEPP), and transdermal estrogen. We selected the non-MHT group as postmenopausal women who had never been prescribed MHT from 2002 to 2019. We compared the incidence of T2DM between the MHT group and the non-MHT group., Results: We enrolled 330,771 women in the MHT group and 798,550 women in the control group. T2DM was diagnosed in 15.2% of the non-MHT group, 16.6% of the tibolone group, 12.1% of the CEPM group, 16.6% of the oral estrogen group, 15.4% of the CEPP group, and 17% of the transdermal estrogen group. In Cox proportional hazard analysis adjusted for variable factors, tibolone, oral estrogen, CEPP, and transdermal estrogen increased the incidence of T2DM. In contrast, there was no change in the risk of T2DM in the CEPM group., Conclusions: MHT, including tibolone, which is currently the most prescribed agent, increased the risk of T2DM; however, CEPM did not increase the risk of T2DM. Only tibolone increased the risk of T2DM in participants older than 70 years., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 by The North American Menopause Society.)

Objectives: With growing incidence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes, more women are expected to spend a larger proportion of their reproductive years living with a diabetes diagnosis. It is important to understand the long-term implications of premenopausal diabetes type on women's reproductive health including their age at natural menopause (ANM)., Methods: Baseline data from the Comprehensive Cohort of Canadian Longitudinal Study on Aging were used. Females who reported premenopausal diagnosis of diabetes were considered exposed. Kaplan-Meier cumulative survivorship estimates and multivariable Cox regression models were used to assess the association between diabetes types and ANM. Sociodemographic, lifestyle, and premenopausal clinical factors were adjusted in the final model as covariates., Results: The sample comprised 11,436 participants, weighted to represent 1,474,412Canadian females aged 45 to 85 years. The median ANM was 52 years. After adjusting for ethnicity, education, smoking, and premenopausal clinical factors, early age of diagnosis of both T1D (<30 years) and T2D (30-39 years) were associated with earlier menopause (T1D, <30: hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.05-2.28; T2D, 30-39: HR, 1.82; 95% CI, 1.12-2.94), as compared with nondiabetics. In addition, later age of diagnosis of T2D (≥40 years) was associated with later ANM (T2D: HR, 0.63; 95% CI, 0.50-0.80). No significant association between gestational diabetes and ANM was noted., Conclusions: Our results point to early menopause among young women living with a diabetes diagnosis. These findings should allow for more focused research geared toward understanding the long-term health implications of diabetes on women's reproductive health and aging., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Abstract: Elastic fibers are present as a thin line around the normal secretory coil of eccrine and apocrine glands, although they are virtually imperceptible with hematoxylin-eosin staining. Skin aging is a consequence of intrinsic and extrinsic factors, and glycation and ultraviolet irradiation are involved in this process favoring elastosis. We report an unusual and prominent perieccrine elastosis on the left temple in the vicinity of a basal cell carcinoma in a 78-year old man with type 2 diabetes, dyslipidemia, and hypertension. Very thick multilamellar and tortuous elastic fibers surrounded the eccrine coils. This increased amount of elastic fibers was confirmed by orcein staining as well as amyloid-P and lysozyme immunostaining. Perieccrine coil elastosis is a very unusual phenomenon that to the best of our knowledge has not been reported. Similar to dermal actinic elastosis, the presence of perieccrine coil elastosis in a skin cancer microenvironment might hypothetically promote tumor growth because of the release of elastin-derived peptides., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs., (© 2022 John Wiley & Sons Australia, Ltd.)

Purpose: Adverse intrauterine environment may predispose offspring to cardio-metabolic dysfunction in later life. In this study, we aimed to investigate the effects of maternal hyperandrogenism (MH) on cardio-metabolic risk factors in female offspring in later life., Methods: This prospective population-based study included 211 female offspring with MH and 757 female offspring without MH (controls). Both groups were followed from baseline to the date of incidence of events, censoring, or end of the study period, whichever came first. Age scaled unadjusted and adjusted cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association of MH with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), overweight and obesity in offspring of both groups. Statistical analysis was performed using the software package STATA; significance level was set at P < 0.05., Results: This study revealed a higher risk of T2DM (unadjusted HR 2.67, 95% CI 1.33-5.36) and overweight (unadjusted HR 1.41, 95% CI 1.06-1.88) in female offspring with MH, compared to controls. Results remained unchanged after adjustment for potential confounders including body mass index, education, physical activity, mother's age at delivery, birth weight, and childhood obesity. However, no significant difference was observed in the risk of pre-DM and obesity in females with MH, compared to controls in both unadjusted and adjusted models., Conclusion: This pioneer study with a long-term follow-up demonstrated that MH increases the risk of developing T2DM and being overweight in female offspring in later life. Further long-term population-based studies are needed to confirm these findings., (© 2021. Italian Society of Endocrinology (SIE).)

Purposes: There is no consensus regarding the optimal bariatric procedure in patients with super obesity [body mass index (BMI) ≥ 50 kg/m 2 ]. This study compared the outcomes of one-anastomosis gastric bypass (OAGB) with those of sleeve gastrectomy (SG) in these patients., Methods: This retrospective study was conducted based on the prospectively maintained data in a cohort of 557 patients with super obesity, who underwent either SG (n = 348) or OAGB with a 200-cm BPL (n = 154) or a 160-cm BPL (n = 55) by the same surgical team from March 2013 to 2017., Results: Patients undergoing OAGB had greater weight loss in comparison to those managed by SG during the first, second, and third years of follow-up. Comparing the OAGB and SG groups within 3 years after surgery, the total weight loss was 36.5 vs. 33.2% (P < 0.001) and the ΔBMI was 20.1 vs. 18.1 kg/m 2 (P < 0.001), respectively. The resolution of diabetes mellitus, hypertension and dyslipidemia were similar after the two procedures. The operative time and length of hospital stay were longer in the OAGB group, and incidence of complications, requiring either readmission or reoperation, was significantly higher after OAGB, in comparison to SG. There was no significant difference in the postoperative weight loss results, resolution of comorbidities, or the incidence of complications between the OAGB-160 and OAGB-200 groups, with the exception of protein-calorie malnutrition requiring revision surgery, which was exclusively observed in the OAGB-200 group., Conclusion: Although OAGB provides superior mid-term weight loss, SG remains the first option for patients with super obesity, due to the safer surgical profile and comparable metabolic improvement., (© 2021. Springer Nature Singapore Pte Ltd.)

Objective: Although menopausal hormone therapy (MHT) is the most effective treatment for menopausal symptoms, menopausal women hesitate to start MHT due to concerns about adverse events. Recently, however, it has been recommended to use it for appropriate patients who have been evaluated for baseline diseases, age, and timing of initiation. We aimed to investigate the association of MHT with cardiovascular diseases (CVDs) and type 2 diabetes among middle-aged postmenopausal women in Korea., Methods: Data were collected from the National Health Insurance Service database in Korea from 2002 to 2016. A total of 58,060 postmenopausal women (including 8,013 [13.8%] MHT users and 50,047 [86.2%] nonusers) were included. The time-dependent Cox regression model with a 1-year latency period was used to evaluate the hazard ratio (HR) and 95% confidence interval (CI) of the associations of MHT with CVDs and type 2 diabetes outcomes. Subgroup analyses by regimen type and cumulative duration were conducted., Results: In the multivariate-adjusted model, MHT was not significantly associated with CVDs (HR = 1.085, 95% CI: 0.899-1.310) or type 2 diabetes (HR = 1.104, 95% CI: 0.998-1.221). Differential effects were not observed by regimen type, cumulative duration, and years since menopause subgroups. Sensitivity analyses also did not show adverse events by MHT on CVDs and type 2 diabetes., Conclusions: Although protective effects of MHT against CVDs or type 2 diabetes were not observed among postmenopausal women who had screened underlying diseases, our results may contribute to reducing the current concerns about the use of MHT for middle-aged postmenopausal women in Korea., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2021 by The North American Menopause Society.)

Aims: Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use., Methods and Results: Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke., Conclusion: In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Obesity and its associated medical problems increase risk of kidney function decline while prior studies suggest that bariatric surgery may improve kidney outcomes. However, little is known about the comparative effectiveness of different types of bariatric surgery on kidney function. In this study, we compare the effects of laparoscopic one anastomosis gastric bypass (LOAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB) on kidney function one year after surgery., Materials and Methods: The patients' demographic, medical, and surgical data were prospectively collected and retrospectively reviewed. Type 2 diabetes mellitus, hypertension, and dyslipidemia, body mass index (BMI), and kidney function tests were obtained before and one year after surgery. Kidney function was evaluated by estimated glomerular filtration rate (eGFR) and spot urine albumin to creatinine ratio (ACR). Changes in eGFR and ACR were compared between LRYGB vs. LOAGB after adjustment for confounders (age, sex, remission of associated medical problems, preoperative BMI, and percentage of excess BMI loss) using ANCOVA model., Results: Both surgical techniques significantly decreased the post-surgery presence of diabetes, hypertension, and dyslipidemia (p < 0.001 for all paired comparisons). The eGFR level significantly increased and the ACR level significantly decreased in both groups (p < 0.001 for all paired comparisons before and after adjustment). However, eGFR and ACR mean differences between LRYGB and LOAGB were not significantly different after adjustment for confounding variables (p = 0.9 and 0.4, respectively)., Conclusion: Both LOAGB and LRYGB improved 1-year eGFR and ACR equally independently from weight loss and other confounders.

Objective: Studies investigating the impact of age at menarche on glucose metabolism disorder have reached inconsistent conclusions, and a quantitative comprehensive assessment of the dose-response association between age at menarche and glucose metabolism disorder has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of glucose metabolism disorder by age at menarche., Methods: MEDLINE via PubMed and EMBASE databases were searched up to March 13, 2019. Restricted cubic splines were used to model the dose-response association., Results: Twenty-five publications (including 34 studies) were included in the meta-analysis. The summary risk ratios (RRs) and 95% confidence limit (CL) per 1-year increase in age at menarche were 0.98 (95% CL 0.98, 0.99) for type 2 diabetes mellitus (T2DM), 0.97 (95% CL 0.96, 0.99) for impaired fasting glucose (IFG), and 0.98 (95% CL 0.97, 0.99) for gestational diabetes mellitus (GDM). We identified linear negative correlations between age at menarche and T2DM (Pnonlinearity = 0.052) and IFG (Pnonlinearity = 0.145), a nonlinear dose-response between age at menarche and GDM (Pnonlinearity = 0.038)., Conclusions: Older age at menarche (range 8-18 years old) is associated with reduced risk of glucose metabolism disorder. The strongest reduction in risk of GDM is observed at menarche age of 14.5 years.

Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk-to-benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post-ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)