Association between FGF-19, FGF-21 and lipocalin-2, and diabetes progression in PCOS

Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF-19, FGF-21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF-19, FGF-21 and lipocalin-2 between subjects with and without PCOS, and to investigate the relationship between the proteins and diabetes progression. In this nested case-control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF-19 (P<0.001) and FGF-21 (P=0.022), but lower lipocalin-2 (P<0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF-19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P=0.026, OR (95% CI): 7.4 (1.3-43.6)), and the positive relationship between FGF-21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P=0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P=0.026, OR (95% CI)): 2.5 (1.1-5.6)), however, this became attenuated after adjusting for waist and fasting glucose (P=0.081). In conclusion, there is differential expression of FGF-19, FGF-21 and lipocalin-2 in PCOS. The serum level of FGF-19, FGF-21 are associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.

Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature

Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55–86%) and restless legs syndrome (8–45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep–wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life. Graphical abstract

Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

<b>Objective:</b> To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody positive (Ab+) relatives of people with type 1 diabetes. <p><b>Methods:</b> We examined 2-hour OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (Mean±SD age: 13.84±9.53 years; BMI-Z-Score: 0.33±1.07; 56.1% male) and 3,720 PTP participants (age: 16.01±12.33 Years, BMI-Z-Score 0.66±1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-Score, HOMA-IR and peak Glucose/C-peptide levels, respectively) were performed. </p> <p><b>Results:</b> In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (p<0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: X²= 25.76 vs. X² = 8.62 and PTP: X²= 149.19 vs. X² = 79.98; all p<0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time.</p> <p><b>Conclusions: </b>In two independent at risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression. </p>

Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

<b>Objective:</b> To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody positive (Ab+) relatives of people with type 1 diabetes. <p><b>Methods:</b> We examined 2-hour OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (Mean±SD age: 13.84±9.53 years; BMI-Z-Score: 0.33±1.07; 56.1% male) and 3,720 PTP participants (age: 16.01±12.33 Years, BMI-Z-Score 0.66±1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-Score, HOMA-IR and peak Glucose/C-peptide levels, respectively) were performed. </p> <p><b>Results:</b> In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (p<0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: X²= 25.76 vs. X² = 8.62 and PTP: X²= 149.19 vs. X² = 79.98; all p<0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time.</p> <p><b>Conclusions: </b>In two independent at risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression. </p>

Blueberry as An Attractive Functional Fruit to Prevent (Pre)Diabetes Progression

Prediabetes, a subclinical impairment between euglycemia and hyperglycemia, is a risk factor for the development of type 2 diabetes mellitus (T2DM) and associated micro- and macrovascular complications. Lifestyle therapy, the first-line treatment of prediabetes, includes physical exercise and dietary regimens enriched in phytochemicals with health-related properties. Blueberries (Vaccinium spp.), given their pleasant taste and great abundance in beneficial phytochemicals, have gained public interest all over the world. Along with a high antioxidant activity, this functional fruit is also well-recognized due to its hypoglycemic and insulin-sensitizing effects and has been recommended for overt T2DM management. Yet blueberries target several other pathophysiological traits, namely gut microbiota dysbiosis and hepatic dysmetabolism, that ensue when prediabetes begins and for which pharmacological interventions tend to be delayed. In this work, we revisited preclinical data from in vitro assays, animal models and human studies, aiming to disclose the potential mechanisms by which blueberries may be a fruitful source of phytochemicals able to prevent (pre)diabetes progression. Collectively, future efforts should focus on longer-term studies with standardized interventions and readouts, particularly in humans, that will hopefully bring more robust evidence and concrete guidance for blueberries’ effective use in prediabetes.