Obstructive sleep apnea (OSA), characterized by recurrent episodes of apnea during sleep and daytime sleepiness, seriously affects human health and may lead to systemic organ dysfunction. The pathogenesis of OSA is complex and still uncertain, but multiple surveys have shown that obesity is an important factor, and the incidence of OSA in people with obesity is as high as 30%. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and may contribute to OSA. Here, we review the most important and representative research results regarding the correlation between obesity-related adipokines including leptin, adiponectin, omentin-1, chemerin, and resistin and OSA in the past 5 years, provide an overview of these key adipokines, and analyze possible intrinsic mechanisms and influencing factors. The existing research shows that OSA is associated with an increase in the serum levels of leptin, chemerin, and resistin and a decrease in the levels of adiponectin and omentin-1; the findings presented here can be used to monitor the development of OSA and obesity, prevent future comorbidities, and identify risk factors for cardiovascular and other diseases, while different adipokines can be linked to OSA through different pathways such as insulin resistance, intermittent hypoxia, and inflammation, among others. We hope our review leads to a deeper and more comprehensive understanding of OSA based on the relevant literature, which will also provide directions for future clinical research.

We had aimed to determine whether homeostasis model assessment–insulin resistance (HOMA-IR) reflects insulin resistance-sensitivity during treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Hyperinsulinemic-euglycemic clamp analysis was performed in 22 patients with type 2 diabetic patients taking dapagliflozin (5 mg/day before or after breakfast). Propensity score matching of these individuals (SGLT2i group) for age, sex, body mass index, and clamp-derived tissue glucose uptake rate with 44 type 2 diabetic patients who had undergone clamp analysis without SGLT2i treatment (control group) identified 17 paired subjects in each group for further analysis of the relation between HOMA-IR and a clamp-derived insulin sensitivity index (ISI). Natural log–transformed HOMA-IR was negatively correlated with ISI in both SGLT2i (r = –0.527, p = 0.030) and control (r = –0.534, p = 0.027) groups. The simple regression lines for log-transformed HOMA-IR and ISI in the two groups showed similar slopes but differed in their intercepts. Multivariate analysis revealed that HOMA-IR for patients with the same ISI in the two groups was related by the formula: HOMA-IR_control = HOMA-IR_SGLT2i × 2.45. In conclusion, HOMA-IR was well correlated with ISI during SGLT2i treatment, but values corresponding to the same ISI were lower in the SGLT2i group than in the control group.

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

This study aimed to analyze the effect of the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) on diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). A total of 322 patients with T2DM participated in this cross-sectional study. OSAHS was diagnosed according to the apnea-hypopnea index (AHI) and it was categorized as follows: normal, mild, moderate, and severe. Relevant clinical data retrieved from medical charts were cross-analyzed between different groups. The relationship between urinary albumin/creatinine ratio(UACR) and OSAHS parameters, which included AHI, lowest oxygen saturation (L-SaO₂), and mean oxygen saturation (M-SaO₂), was evaluated by partial correlation analysis. DN stages were classified into a non-DN group, a microalbuminuria group, and a macroalbuminuria group. Multiple factor logistic regression analysis was employed to analyze factors influencing DN. The results showed that mild OSAHS, moderate OSAHS, and severe OSAHS patients had a higher Body mass index (BMI), creatinine (CR) level, UACR, and a longer duration of T2DM (p < 0.05) than the non-OSAHS group. The prevalence of DN in the non-OSAHS, mild OSAHS, moderate OSAHS, and severe OSAHS groups was 18.4%, 19.2%, 34.6%, and 49.4%, respectively (p < 0.05). Multiple factor logistic regression analysis revealed that systolic blood pressure (SBP) (OR = 1.03), AHI (OR = 1.02), and duration of T2DM (OR = 1.04) were correlated with DN (p < 0.05). These findings revealed that OSAHS is highly prevalent in T2DM and AHI is independently associated with the presence of DN.

Obesity is a major risk factors for type 2 diabetes, and weight loss is beneficial to diabetic patients who are obese or overweight. Dipeptidyl peptidase-4 (DPP-4) inhibitors are anti-diabetic drugs. Although it has been known that the effect of most of the DPP-4 inhibitors on body weight is neutral, several studies suggested that some DPP-4 inhibitors suppressed body weight. Nonetheless, the mechanisms underlying DPP-4 inhibitor-induced weight loss are not fully understood. In this study, the mice fed high-fat high sucrose diet (HFHSD) containing a DPP4 inhibitor, anagliptin, showed reduced food intake and body weight compared to the mice fed non-treated HFHSD, but oxygen consumption and respiratory exchange ratio (RER) were not altered. Sequential administration of leptin suppressed food intake and body weight more apparently in anagliptin treated HFHSD fed mice than non-treated HFHSD fed mice. Oxygen consumption and RER were comparable between anagliptin treated and non-treated mice after leptin administration. The number of phospho STAT3 expressed cells in the arcuate nucleus after leptin administration was increased in anagliptin treated mice compared to non-treated mice. These data suggested that anagliptin ameliorated leptin resistance induced by HFHSD and thereby decreased food intake and body weight. These effects of anagliptin could be beneficial to the treatment of obese diabetic patients.

Previously, we reported that short-term continuous glucose monitoring (CGM) with the professional iPro2^© CGM device is a good clinical indicator of glycated hemoglobin (HbA1c) levels. However, there was no significant correlation between CGM and HbA1c levels when HbA1c levels were >8.0%. To further investigate this issue, we performed a similar study using the FreeStyle Libre Pro^©, a newer device that does not require glucose calibration and allows patients to be examined for up to 14 days. Fifty-nine patients (68% women, 32% men) were examined. Twenty-eight and 31 patients presented with type 1 and type 2 diabetes, respectively. Clinically assessed HbA1c levels were compared to blood glucose levels determined by the FreeStyle Libre Pro^© for up to 14 days (10.7 ± 3.7 days). We found a significant correlation between HbA1c and CGM levels even when HbA1c levels were >8.0%. Additionally, the correlation between HbA1c and average glucose was identified with the modern CGM and was found to deviate substantially from the new suggested formula. More importantly, we found a more robust correlation between HbA1c and CGM levels in patients with type 2 diabetes. Overestimation or underestimation of blood glucose levels through CGM might increase the risks of inappropriate clinical treatment of diabetes patients. Our results indicate the need for proper CGM data interpretation individualized for each patient to better assist the determination of customized treatments for patients.

The Abbott FreeStyle Libre flash glucose monitoring system (FGM) is a recently introduced, but widespread continuous glucose monitoring system. While its mean absolute relative difference (MARD) value indicating its accuracy is acceptable with reference to the self-monitoring of blood glucose (SMBG) levels, few reports have examined the MARD in sensor glucose values of FGM (FGM-SG) with reference to plasma glucose (PG) levels and the factors determining it. We performed oral glucose tolerance tests (OGTTs) in 25 Japanese subjects without diabetes. Parkes error grid analyses showed that FGM-SG with either SMBG or PG levels as a reference met International Organization for Standardization criteria. The MARD in FGM-SG with reference to SMBG levels was 10.9 ± 4.1% during OGTTs. Surprisingly, the MARD in FGM-SG with reference to PG levels was 20.3 ± 10.3% during OGTTs, revealing a discrepancy in the accuracy of FGM-SG compared with that of PG levels; moreover, the MARD showed negative correlations with fasting blood sugar level, homeostasis model assessment insulin resistance index, and body mass index (BMI). Multiple regression analyses revealed that BMI contributed the most to the MARD when FGM-SG and PG level were compared, as lean individuals have a greater MARD regardless of glucose levels. Inaccurate FGM data could potentially increase the risk of inappropriate treatment; consideration of such factors is critical to ensure reliable FGM values.

Vascular endothelial growth factor (VEGF) is one of main regulators of angiogenesis that functions by binding to its receptors, including VEGF receptor (VEGFR) 2. There are few data available regarding the association between VEGF and VEGFR polymorphisms and the susceptibility to and prognosis of autoimmune thyroid diseases (AITDs). To elucidate this association, we genotyped four functional VEGF and two VEGFR2 polymorphisms and measured serum VEGF levels. In the four functional VEGF polymorphisms, the frequencies of the I carrier and I allele of VEGF –2549 I/D, which has lower activity, were higher in patients with severe HD than in those with mild HD. In the two functional VEGFR2 polymorphisms, the frequency of the rs2071559 CC genotype, which has higher activity, was higher in patients with intractable GD than in controls, and the proportion of GD patients with larger goiters was higher in those with the CC genotype. Moreover, the frequency of the rs1870377 TT genotype with higher activity was higher in patients with intractable GD than in those with GD in remission. Combinations of VEGF and VEGFR2 polymorphisms with stronger interactions were associated with the intractability of GD. Serum VEGF levels were higher in HD and AITD patients than those in controls. In conclusion, VEGF polymorphisms with lower activity were associated with the severity of HD, while VEGFR2 polymorphisms and the combinations of VEGF and VEGFR2 polymorphisms, which have stronger interactions, were associated with the intractability of GD. VEGF and VEGFR2 polymorphisms were associated with HD severity and GD intractability, respectively.

The results of studies on the relationship between cytokine polymorphisms and polycystic ovary syndrome (PCOS) have been controversial. This meta-analysis was thus designed to more precisely assess the relationship between TNF-α/IL-1/IL-6/IL-10 polymorphisms and PCOS by pooling the results of published studies. A search of PubMed, Embase, Web of Science, and CNKI databases turned up 23 studies that were pooled and analyzed in this meta-analysis. The overall results showed that the distributions of TNF-α –238 G/A, TNF-α –857 C/T, and IL-1B –51 C/T polymorphisms among patients and controls differed significantly. Additionally, the distributions of TNF-α –308 G/A and IL-1B –51 C/T polymorphisms among patients and controls from Asian populations differed significantly, whereas the distributions of IL-6 –174 G/C and IL-1A –889 C/T polymorphisms among patients and controls from Caucasian populations also differed significantly. In conclusion, our meta-analysis demonstrated that TNF-α –238 G/A, TNF-α –857 C/T, and IL-1B –51 C/T polymorphisms might influence susceptibility to PCOS in the overall pooled population. Moreover, TNF-α –308 G/A and IL-1B –51 C/T polymorphisms might influence susceptibility to PCOS in Asians, whereas IL-6 –174 G/C and IL-1A –889 C/T polymorphisms might influence susceptibility to PCOS in Caucasians.

Subacute thyroiditis is a self-limited inflammatory disease and very few patients undergo ultrasonographic re-examination if no nodules are found at the initial examination. The objective of the study was to assess the diagnostic accuracy of ultrasonography in detecting nodular lesions in patients with subacute thyroiditis. We conducted a longitudinal study involving 710 patients with subacute thyroiditis who underwent ultrasonographic examinations in a single center between 2008 and 2018. These examinations were performed at initial diagnosis and during follow-up, with subsequent evaluation of nodules using fine needle aspiration cytology. Ultrasonographic examination used for the initial screening of thyroid nodules in patients with subacute thyroiditis showed a sensitivity of 72.4%, specificity of 89.0%, positive predictive value of 80.4%, and negative predictive value of 83.8%. Twenty-two patients (3.1%) had concomitant papillary thyroid carcinoma, 10 of whom underwent thyroidectomy while the remaining 12 opted for active surveillance owing to having low-risk microcarcinomas. Approximately 30% of papillary carcinomas (7/22) were identified during follow-up ultrasonography, but not during the initial scan. All tumors in this false-negative group were latently localized in the bilateral hypoechoic regions of the thyroid and showed no calcified components. Of the 15 tumors that were detected during both initial and follow-up examinations, 7 exhibited calcified components and 5 were located in unaffected areas apart from the inflammatory hypoechoic region. Subacute thyroiditis highly obscures any coexisting papillary carcinoma when inflammatory hypoechoic regions are present. Ultrasonographic re-examination after a sufficient interval is indispensable for patients with subacute thyroiditis.