Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver condition affecting 25%-40% of the worldwide population. NAFLD is traditionally related to obesity and metabolic disorders. NAFLD can also affect non-obese individuals, termed "lean NAFLD" (LN), who exhibit a paradoxical combination of physical leanness and metabolic obesity. Factors contributing to LN remain unclear, necessitating further research. This analysis aims to understand LN's prevalence and metabolic characteristics compared to obese NAFLD (ON) populations.

Methods: This meta-analysis searched various databases until August 1, 2023. Inclusion criteria involved observational studies comparing LN with overweight/obese NAFLD. Data extraction included baseline characteristics, disease occurrence, metabolic profile, and clinical parameters-statistical analysis employed calculating risk ratios (RR) and standard mean differences.

Results: Twenty-five studies were analyzed. LN is associated with lower prevalence in both NAFLD (RR 0.27, 95% confidence interval (CI) 0.14-0.52, p = <0.0001) and total (RR 0.27, 95% CI 0.15-0.51, p < 0.0001) population. LN had lower diabetes mellitus (RR 0.78, 95% CI 0.71-0.87, p < 0.00001), dyslipidemia (RR 0.87, 95% CI 0.79-0.95, p = 0.002), hypertension (RR 0.80, 95% CI 0.74-0.87, p < 0.00001), and metabolic syndrome (RR 0.45, 95% CI 0.31-0.64, p < 0.00001) compared to those with ON. The LN group's lipid profile, blood pressure, and other clinical parameters were favorable compared to ON.

Conclusion: The prevalence of NAFLD among lean and non-lean individuals varies by region. Our analysis revealed that LN is associated with lower metabolic diseases, fasting blood sugar, blood pressure, and a more favorable lipid profile compared to ON.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) has revolutionised the care of people with diabetes but its uptake and benefits in older adults are not well known. We examined the impact of isCGM (Freestyle Libre, FSL) on glycaemic outcomes in younger (⩽65 years) and older adults (>65 years) with diabetes.

Design and methods: In total, 2260 adult patients registered on the Libreview account at University Hospitals Birmingham NHS Foundation Trust, UK, were included. Inclusion criteria: all patients with type 1 and type 2 diabetes aged >18 years, use of isCGM >6 months, scanning at least 6 times/day. Demographics, diabetes history and glycaemic outcomes (time in range (TIR), time above range and time below range (TBR), estimated HbA1c, HbA1c at start and at end of study) were collected by accessing electronic patient records and Libreview. Outcomes were compared between age groups ⩽65 or >65 years old.

Results: Most patients were of Caucasian ethnicity (⩽65 years 68%, >65 years 73%) and had type 1 diabetes. Mean duration of diabetes was 19.5 years (range 0-65 years) and 34.5 years (range 0-79 years) for ⩽65 and >65 years, respectively. Only a quarter of those ⩽65 years achieved (219/943; 23.2%) their age specific TIR target compared to 69% (78/113) of those >65 years cohort, while 70.1% (663/946) of ⩽65 years and 40.7% (46/113) of >65 years achieved their age-specific TBR target. When the less strict ⩽65 years TBR target was applied, 75% (85/113) of >65 years cohort achieved this.

Conclusion: FSL use was associated with improved glycaemic outcomes across all age groups. Individualised targets may be needed to improve TBR in those aged >65 years.

Background: Fat distribution plays an important role in impaired glucose tolerance. Android adiposity (ANDROID) and gynoid adiposity (GYNOID) have been proven to be linked with insulin resistance. A higher risk of sarcopenia is associated with type 2 diabetes mellitus (T2DM). In this study, ANDROID, GYNOID, and ANDROID to GYNOID ratios (A/G ratios) were evaluated in T2DM patients to determine if they were associated with sarcopenia.

Methods: We recruited 1086 T2DM patients, measured skeletal muscle index (SMI), ANDROID, GYNOID, and collected clinical data.

Results: T2DM patients with 119 male subjects had sarcopenia (20.24%), and 72 female subjects had sarcopenia (16.51%). All patients with T2DM who had high ANDROID and A/G ratios were at a reduced risk of sarcopenia. The SMI showed a correlation with ANDROID and A/G ratios among subjects with T2DM.

Conclusion: ANDROID and A/G ratios are inversely related to sarcopenia in T2DM patients.

Graves' disease (GD) is the most common cause of hyperthyroidism while Hashimoto or autoimmune thyroiditis is the most common cause of hypothyroidism. Spontaneous hypothyroidism may develop after successful medical treatment of GD in up to 20% of cases. This report presents a gentleman who is a known smoker and was diagnosed with GD at the age of 64 years. He was counseled about smoking cessation and started with medical treatment using carbimazole (CBZ). He was adequately controlled using medical treatment, yet he continued to smoke. After 2 years of medical treatment, CBZ was stopped due to developing hypothyroidism on the minimum dose of treatment. Celebrating the discontinuation of treatment, the patient decided to quit smoking. One month later, he was euthyroid; however, 4 months later, he developed overt hypothyroidism. He received levothyroxine replacement therapy and titrated to achieve euthyroidism and remained on levothyroxine for more than 5 years. The possibility that quitting smoking may have triggered the development of hypothyroidism was raised due to the coincidence of developing hypothyroidism only 4 months after quitting smoking. Current smoking is associated with a higher risk of developing both GD and Graves' orbitopathy. Quitting smoking is associated with a higher risk of developing new-onset thyroid autoimmunity. Quitting smoking is also associated with a sevenfold higher risk of autoimmune hypothyroidism especially in the first year of smoking cessation. Involved mechanisms may include a sudden increase in oxidative stress, a sudden increase in iodide delivery to thyroid follicles, or promoting T-helper 1-mediated autoimmune thyroiditis after quitting smoking. The present case suggests that quitting smoking may be a triggering factor for the development of hypothyroidism following successful medical treatment of GD, a phenomenon that may affect one-fifth of GD patients without previously reported triggers.

Background: Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index <18.5 kg/m²) and normal-weight (body mass index of 18.5-24.9 kg/m²) adult Ugandans with new-onset nonautoimmune diabetes.

Methods: We collected the demographic, clinical, anthropometric, and metabolic characteristics of 160 participants with nonobese new-onset type 2 diabetes (defined as diabetes diagnosed <3 months, body mass index <25 kg/m², and absence of islet-cell autoimmunity). These participants were categorized as underweight and normal weight, and their phenotypic characteristics were compared.

Results: Of the 160 participants with nonobese new-onset type 2 diabetes, 18 participants (11.3%) were underweight. Compared with those with normal weight, underweight participants presented with less co-existing hypertension (5.6% versus 28.2%, p = 0.04) and lower median visceral fat levels [2 (1-3) versus 6 (4-7), p < 0.001], as assessed by bioimpedance analysis. Pathophysiologically, they presented with a lower median 120-min post-glucose load C-peptide level [0.29 (0.13-0.58) versus 0.82 (0.39-1.50) nmol/l, p = 0.04] and a higher prevalence of insulin deficiency (66.7% versus 31.4%, p = 0.003).

Conclusion: This study demonstrates that nonautoimmune diabetes occurs in underweight individuals in sub-Saharan Africa and is characterized by the absence of visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency. These findings necessitate further studies to inform how the prevention, identification, and management of diabetes in such individuals can be individualized.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.