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This mini review explores the increasing prevalence of obesity in type 1 diabetes (T1D) and the challenges patients face in achieving optimal glycemic control with current treatments. It discusses the evidence supporting the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) as potential adjunctive therapy in T1D to reduce weight and improve insulin resistance. Potential benefits need to be weighed against the risk of hypoglycemia and lack of long-term data. [ABSTRACT FROM AUTHOR]

Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy. Objective Our study sought to assess the economic burden associated with EndoCA in PCOS. Method Using PRISMA systematic review guidelines, we evaluated studies on EndoCA rates in patients with PCOS. Excluded studies were reviews and case reports, those with nonhuman subjects, without controls, without full text available, or reporting solely on other conditions. Selected studies were assessed for quality using the Newcastle-Ottawa Scale. Meta-analysis used DerSimonian-Laird random effects model to assess pooled risk ratio (RR). Excess cost was assessed in US dollars (USD). Result Of 98 studies screened, 9 were included. Pooled RR for EndoCA in PCOS was 3.46 (95% CI, 2.28-5.23), P ≤.001. In the United States, prevalence of EndoCA in patients with PCOS in 2020 was 1.712%, compared with a baseline estimated prevalence in all women of 0.489%. The excess prevalence of EndoCA attributable to PCOS was 1.223%, approximately 98 348 affected women. A population attributable fraction of EndoCA for PCOS was 24.4%. Given estimated costs of EndoCA exceeding $1.9 billion (in 2023 USD), the economic burden of EndoCA attributable to PCOS exceeds $467 million/year. Conclusion The excess annual US healthcare cost for EndoCA attributable to PCOS exceeds $467 million/year (2023 USD). Although a concerning morbidity of PCOS, it is notable that the economic burden of EndoCA attributable to the disorder represents only a small fraction of its total healthcare burden. [ABSTRACT FROM AUTHOR]

Background and Aims: Recently, a new entity was introduced, MetALD, which includes patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), who consume moderate amounts of alcohol. However, little is known regarding the metabolic and clinical characteristics of these patients. Methods: Data from the National Health and Nutrition Examination Surveys 2017–2020 was used. Participants without valid transient elastography (TE) measurements, incomplete alcohol consumption report, or with alternative etiologies of liver steatosis were excluded. Results: A total of 6901 patients were included in the study, of which 106 (1.5%) had MetALD. Overall, MetALD patients showed a metabolic profile that was more similar to patients with alcohol related liver disease (ALD) than MASLD. Specifically, while patients with MetALD showed values in‐between MASLD and ALD for body mass index (BMI), aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT) and haemoglobin A1c, they had similar high‐density lipoprotein cholesterol (HDL‐C), blood pressure, prevalence of diabetes and insulin resistance to ALD patients. Increasing alcohol consumption was associated with lower insulin resistance and A1c and higher triglycerides, HDL‐C and blood pressure. Moreover, while AST, ALT and GGT increased with alcohol consumption, this did not translate into worse hepatic steatosis or liver fibrosis by TE. Conclusions: MetALD patients share some characteristics with MASLD, but they resemble ALD patients more, especially after adjusting for BMI. Alcohol consumption produces a dissociation between insulin resistance and some cardiometabolic risk factors (blood pressure and HDL‐C), which may make the current classification of patients challenging. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) in young compared with older adults. Methods: Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated. Results: A total of 243 participants were ages <45 years, and 1177 were ages ≥45 years. Obesity, T2D, and metabolic syndrome were highly prevalent in young adults. Frequencies of steatosis and fibrosis were high in young adults (50.2% and 7.5% vs. older adults 52.7% and 9.9%, respectively) and were significantly higher in those with both obesity and T2D (71.1% and 15.7%, respectively; p < 0.01). In young adults, T2D and obesity were the strongest risk factors for hepatic fibrosis (odds ratios 4.33 [95% CI: 1.37–13.68] and 1.16 [95% CI: 1.07–1.25], respectively; p < 0.05). Conclusions: There is a high prevalence of clinically significant hepatic fibrosis in young adults with cardiometabolic risk factors. Up to one in seven young adults with obesity and T2D had clinically significant hepatic fibrosis on elastography. This highlights the need to screen young adults with cardiometabolic risk factors for MASLD for early detection and intervention. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOS) is a common female cardiometabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. Objective To determine the association between the prevalence of PCOS and obesity. Materials and methods A systematic review was conducted to identify population studies on PCOS prevalence globally through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institutes of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality. Results Fifty-eight studies with 85 956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria. Conclusion The prevalences of PCOS and obesity appear to be modestly associated, although our data cannot establish causality. This study also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the performance of noninvasive tests (NITs) across different racial and ethnic groups in a large multiethnic cohort. Methods: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 2017 through 2020. Participants without valid transient elastography measurements or with alternative etiologies of liver steatosis disease were excluded from the study. Results: Among the 6359 adults included in the study, fatty liver index and nonalcoholic fatty liver disease liver fat scores performed well for the prediction of metabolic dysfunction‐associated steatotic liver disease, without significant changes across racial and ethnic groups. However, significant differences were observed across racial and ethnic groups for the prediction of advanced fibrosis and cirrhosis. The fibrosis‐4 (FIB‐4) index, aspartate aminotransferase to platelet ratio index (APRI), and nonalcoholic fatty liver disease fibrosis score underperformed in non‐Hispanic Black patients for the detection of cirrhosis. For the detection of advanced fibrosis, their performance was also numerically worse in non‐Hispanic Black patients but only reached statistical significance for APRI. Using a cutoff point of 12 kPa for advanced fibrosis, both APRI and the FIB‐4 index performed significantly worse in non‐Hispanic Black patients. Conclusions: In a large, diverse national cohort, the performance of NITs was overall poor compared with transient elastography, and NITs showed differences across racial and ethnic groups. Given the widespread use of NITs, it is imperative that the scores are equitable across racial and ethnic groups. [ABSTRACT FROM AUTHOR]

Purpose Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. Methods We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. Results Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. Conclusion AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field. [ABSTRACT FROM AUTHOR]

The article is a response to a letter from Drs. de Zegher and Ibáñez regarding the role of adipose tissue dysfunction in polycystic ovary syndrome (PCOS). The authors of the response agree with the doctors' belief that dysfunctional adipose tissue is central to PCOS and contributes to hyperinsulinemia and ectopic fat accumulation. They explain that their review focused on the mechanisms of adipose tissue dysfunction and did not extensively cover therapeutic options for managing PCOS. They also discuss the limitations of oral contraceptives in treating PCOS and the potential benefits of combination therapy with flutamide, metformin, and pioglitazone. The authors caution against prematurely extrapolating the results of studies on spironolactone and suggest that more research is needed to understand its role in modulating adipose tissue. They conclude by emphasizing the importance of addressing adipose tissue dysfunction in PCOS and the need for further studies on the effects of various medications on this dysfunction. [Extracted from the article]