High-normal free thyroxine level is related with decreased bone mineral density in nonobese male patients with type 2 diabetes over 50 years old.

Background: The prevalence of 'low bone mineral density (BMD)' in Type 2 diabetes (T2DM), especially stratified by body mass index, is seldom reported. The relation of the euthyroid range and low BMD in T2DM remains to be further elucidated. Objectives: We aim to investigate the thyroid hormones' impact on BMD among euthyroid patients with T2DM. Design and methods: A total of 1452 hospitalized T2DM patients with normal thyroid function (43.6% males aged over 50 and 56.4% postmenopausal females) were enrolled in this cross-sectional study. BMD was measured at lumbar spine by GE lunar dual-energy X-ray absorptiometry system, and 'low BMD' was defined as T-score <-1.0 SD. The prevalence of 'low BMD' was compared between obese and nonobese (body mass index < 25 kg/m2) groups for both sexes, and the relation of low BMD and free T4 quartiles was explored by multiple logistic regression. Results: The general prevalence of 'low BMD' was 12.3% for male patients aged over 50 (15.5% in the nonobese group and 8.0% in the obese group) and 49.8% for postmenopausal females (56.7% in the nonobese group and 48.9% in the obese group). After adjustment in multiple linear regression, free T4 level remained significantly related to decreased BMD in nonobese male subgroup. Multiple logistic regression revealed that BMD of the highest free T4 quartile (1.12-1.48 ng/dL) decreased significantly than other three quartiles after adjusting for confounding factors including age, body mass index, serum calcium and creatinine level, fasting glucose, alkaline phosphatase, glycosylated hemoglobin, total cholesterol, and smoking history (OR = 2.724, 95% CI = 1.085-6.840, p = 0.033). No significant relation was found in obese male or postmenopausal female groups. Conclusion: High-normal free T4 is a potential independent risk factor for 'low BMD' in nonobese male T2DM patients aged over 50. Close attention should be paid to thyroid function profile, even within normal range, in nonobese men with underlying higher fracture risks on diabetes status.

Metabolic Syndrome and Its Components Are Associated With Altered Amino Acid Profile in Chinese Han Population.

Objective: Recent studies have found that the levels of plasma amino acids, such as branched-chain amino acids and aromatic amino acids, were associated with visceral obesity, insulin resistance, future development of diabetes and cardiovascular diseases. However, few studies have involved a Chinese Han population. This study aimed to examine the association between amino acid profile and metabolic syndrome (MetS) and its components in the Chinese Han population. Methods: This is a cross-sectional study, which enrolled a cohort of 473 participants from a community. We employed the isotope internal standard method to determine the plasma concentrations of 28 amino acids using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). Participants were divided into MetS (n = 72) and non-MetS groups (n = 401) to analyze the association between amino acids and MetS and its components. Results: The prevalence of MetS was 15.2% according to the criteria. Plasma concentrations of isoleucine (Ile), leucine (Leu), valine (Val), tyrosine (Tyr), tryptophan (Trp), phenylalanine (Phe), glutamic acid (Glu), aspartic acid (Asp), alanine (Ala), histidine (His), methionine (Met), asparagine (Asn), and proline (Pro) were significantly higher in the MetS group than those in the non-MetS group (P < 0.05), but taurine (Tau) was significantly lower (P < 0.05). When MetS components were increased, the concentrations of these 13 amino acids significantly increased (P < 0.05), but Tau concentration was significantly decreased (P < 0.05). We extracted the amino acid profile by principal component analysis (PCA), PC1 and PC2, which extracted from the 14 amino acids, were significantly associated with MetS (odds ratio, 95% confidence interval: 1.723, 1.325-2.085 and 1.325, 1.043-1.684, respectively). A total of 260 non-MetS participants were followed up effectively, and 42 participants developed new-onset MetS within 5 years. We found that the amino acid profile of PC1 was linked to the occurrence of future MetS. Decreased Tau was correlated with the future development of MetS. Conclusion: Participants with MetS exhibit an abnormal amino acid profile, and its components gradually increase when these amino acids are altered. Amino acid PCA profile can be employed for assessing and monitoring MetS risk. Finally, decreased Tau may be linked to the future development of MetS.

Risk factors for residual dizziness in patients successfully treated for unilateral benign posterior semicircular canal paroxysmal positional vertigo.

OBJECTIVE: The risk factors for residual dizziness (RD) after successful treatment of benign paroxysmal positional vertigo (BPPV) are poorly characterized. We determined the risk factors for RD in patients with benign unilateral posterior semicircular canal paroxysmal positional vertigo (pc-BPPV) after successful treatment. METHODS: We conducted a prospective study of patients diagnosed with unilateral pc-BPPV between March 2015 and January 2017. Bone mineral density (BMD) was measured by dual-energy X-ray bone mineral densitometry. Participants underwent bithermal caloric testing (C-test) using videonystagmography and a canalith repositioning procedure (CRP). The occurrence of RD was the primary outcome. The participants underwent follow-up 1 week, 1 month, and 1 year after successful CRP, consisting of outpatient visits, questionnaires, and telephone interviews. RESULTS: We assessed 115 participants with unilateral pc-BPPV (31 men and 84 women) who were 53.2 ± 8.8 years old. RD occurred in 60 (52.2%) participants. The participants who experienced RD were older, had vertigo for longer before treatment, and were more likely to show a positive C-test and significant BMD loss. CONCLUSIONS: We found that a significant reduction in BMD (T-score < -1 standard deviation), a positive C-test, and older age are independently associated with RD in patients with pc-BPPV after successful CRP.

[Identification of a novel DGUOK variant in a Chinese family affected with mitochondrial DNA depletion syndrome].

OBJECTIVE: To explore the molecular etiology for a Chinese family with mitochondrial DNA depletion syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents.Targeted capture and next-generation sequencing was carried out to detect potential variants. Suspected variant was validated by Sanger sequencing. RESULTS: A novel homozygous frameshift variant c.505_508delTATC was identified in the patient, for which both his mother and father were carriers. CONCLUSION: The frameshift variant c.505_508delTATC probably underlies the mitochondrial DNA depletion syndrome in this patient. The result also enriched the variant spectrum of DGUOK gene.

Prevalence of macro- and microvascular complications in patients with type 2 diabetes and kidney disease with or without albuminuria in a single Chinese Diabetes Centre.

OBJECTIVE: To investigate the relationship between diabetic retinopathy, neuropathy and low ankle-brachial index in mild-to-moderate chronic kidney disease of type 2 diabetic patients. METHODS: We enrolled 875 type 2 diabetic patients who were divided into two phenotypes (with or without albuminuria) and stratified into three groups (stage 1 with estimated glomerular filtration rate ⩾ 90 mL/min/1.73 m(2), stage 2 with estimated glomerular filtration rate of 60-89, stage 3 with estimated glomerular filtration rate of 30-59). The prevalence of diabetic retinopathy, neuropathy and low ankle-brachial index was compared and the risk factors of renal impairment were determined. RESULTS: Among chronic kidney disease stages, the prevalence of diabetic retinopathy increased from 42.5%, 56.6% to 66.7% in albuminuric subjects and from 29.4%, 33.0% to 50.0% with no significant trend in normoalbuminuric subjects (p = 0.005, 0.007 and 0.399 compared with albuminuric subjects in each stage). There was a significantly increased prevalence of low ankle-brachial index (17.5%, 22.6% and 44.4%) in normoalbuminuric subjects but no significant trend in albuminuric subjects. Diabetic retinopathy (odds ratio = 2.474, 95% confidence interval = 1.009-6.068) was an independent risk factor of declining kidney function in albuminuric patients. CONCLUSION: The prevalence of diabetic retinopathy was graded according to the estimated glomerular filtration rate declining in albuminuric patients while the prevalence of low ankle-brachial index was gradually increased in normoalbuminuric patients, indicating the diverse underlying mechanisms of mild to moderate chronic kidney disease between these two phenotypes.

Low ankle-brachial index is associated with early-stage chronic kidney disease in type 2 diabetic patients independent of albuminuria.

AIMS: The role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60-89 ml/min/1.73 m2 of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR. METHODS: The cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥ 90 mL/min/1.73 m2 and the lower group with eGFR of 60-89. ABI was categorized as normal (1.0-1.39), low-normal (0.9-0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD. RESULTS: The prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188-4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors. CONCLUSIONS: There was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.

Correlation between the amplitude of glucose excursion and the oxidative/antioxidative system in subjects with different types of glucose regulation.

OBJECTIVE: To investigate effects of glucose excursion on the oxidative/antioxidative system in subjects with different types of glucose regulation. METHODS: A total of 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR) and 27 subjects with newly diagnosed type 2 diabetes mellitus (T2DM) were selected and recruited for 3 days' continuous glucose monitor system (CGMS) assessment. The data from CGMS was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), area under the ROC curve when the blood glucose >5.6 mmol/L within 24 h (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE). In all groups, the content or activity of malondialdehyde (MDA), total antioxidation capacity (TAOC) and glutathione peroxidase (GSH-Px) were detected. RESULTS: Glucose excursion parameters of subjects with T2DM or IGR were higher than those of NGR subjects (P<0.05 or 0.01). Moreover, Glucose excursion parameters of T2DM subjects were higher than those of IGR subjects (P<0.05 or 0.01). Subjects with T2DM or IGR had significant higher MDA levels and lower GSH-Px/MDA and TAOC/MDA levels compared to NGR subjects (P<0.01). T2DM subjects had even higher MDA levels and lower GSH-Px/MDA levels than IGR (P<0.05 or 0.01). According to the median of normal population for MAGE, T2DM and IGR subjects were divided into MAGE>2.6mmol/L Group and MAGE ≤ 2.6mmol/L Group. MAGE>2.6mmol/L Group had higher levels of MDA and lower levels of GSH-Px/MDA than MAGE ≤ 2.6mmol/L Group (P<0.05). There was no significant difference between the two groups (P>0.05) in terms of the levels of TAOC/MDA. Pearson correlation analysis showed that MDA was positively correlated with FPG, 2hPG, MAGE, and SBP. GSH-Px/MDA was negatively correlated with MAGE and TC. TAOC/MDA was negatively correlated with FPG. Partial correlation analysis showed that the relationship between MDA and MAGE, GSH-Px/MDA, and MAGE remained significant after adjustments for the other differences among groups. CONCLUSION: Glucose excursion contributed significantly to promoting lipid peroxidation and decreasing antioxidation capacity than chronic sustained hyperglycemia did in the subjects with different types of glucose regulation.

Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation.

The effect of glucose excursions on oxidative stress is an important topic in diabetes research. We investigated this relationship by analyzing markers of oxidative stress and glycemic data from a continuous glucose monitoring system (CGMS) in 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR), and 27 patients with newly diagnosed type 2 diabetes (T2DM). We compared the mean amplitude of glycemic excursion (MAGE), mean postprandial glucose excursion (MPPGE), and mean postprandial incremental area under the curve (IAUC) with plasma levels of oxidative stress markers 8-iso-PGF2α, 8-OH-dG, and protein carbonyl content in the study subjects. Patients with T2DM or IGR had significantly higher glucose excursions and plasma levels of oxidative stress markers compared to normal controls (P < 0.01 or 0.05). Multiple linear regression analyses showed significant relationships between MAGE and plasma 8-iso-PGF2α, and between MPPGE and plasma 8-OH-dG in patients with IGR or T2DM (P < 0.01 or 0.05). Furthermore, 2h-postprandial glucose level and IAUC were related to plasma protein carbonyl content in the study cohort including T2DM and IGR (P < 0.01). We demonstrate that glucose excursions in subjects with IGR and T2DM trigger the activation of oxidative stress.

[Correlation between the amplitude of glucose excursion and plasma 8-iso prostaglandin F2alpha level in subjects with different types of glucose regulation].

OBJECTIVE: To investigate the effect of glucose excursion on oxidative stress that is expressed by plasma 8-iso prostaglandin F2alpha (8-iso) level. METHODS: Continuous glucose monitor system (CGMS) was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25 patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma 8-iso level was determined by EIA. RESULTS: The plasma 8-iso level of the T2DM patients was 230 ng/L, significantly higher than that of the subjects with IGR (199 ng/L, P < 0.05) and that of the NGR subjects (156 ng/L, P < 0.01). Patients with T2DM also had higher levels of glycated hemoglobin (HbA1c), MBG, SDBG, 1 h pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P < 0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the IGR subjects were all significantly higher than those of the NGR individuals (P < 0.05 or 0.01). Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG, 1 h pre-PG, 3 h PPG, MODD, and HbA1c in all groups. Further analysis showed that the relationship between plasma 8-iso level and MAGE remained significant after adjustment for the other parameters of glucose excursion in multiple linear regression analysis (multiple R(2) = 0.55 for the model including MAGE). Standardized regression coefficients were 0.694 (P = 0.000) for MAGE. CONCLUSION: Glucose excursion exhibits a stronger triggering effect on oxidative stress than chronic sustained hyperglycemia in the subjects with IGR and T2DM.