Time in range of glucose and sarcopenia in elderly patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the relationship between time in range(TIR) of glucose and sarcopenia in elderly patients with type 2 diabetes mellitus.Methods:A total of 673 patients with type 2 diabetes aged 65 years and above who were admitted to Henan Provincial People′s Hospital from March 2018 to July 2020 were selected. All patients completed questionnaire, physical and laboratory examination. Sensor-based flash continuous glucose monitoring(CGM) systems was used to monitor glucose levels, and the TIR was computed. Dual energy X-ray was used to assess total muscle mass and appendicular skeletal muscle mass index(ASMI) was calculated, the muscle strength was assessed with testing handgrip strength, and physical function was assessed by testing gait speed. Sarcopenia was diagnosed and graded according to the 2019 Asian Working Group on Sarcopenia(AWGSOP) standard. Patients with less than 3 days of CGM were excluded and a total of 658 subjects were included in the analysis.Results:The total prevalence of sarcopenia was 28.72%. Compared with non-sarcopenia group, TIR levels in the sarcopenia and severe sarcopenia groups were significantly decreased [55.0%(36.5%, 68.0%), 49.0%(31.0%, 70.5%) vs 66.0%(44.8%, 79.0%), both P<0.01]. The level of ASMI increased in line with TIR quartiles and topped in the fourth quartile group( P<0.05). Pearson correlation analysis showed that TIR was significantly positively correlated with ASMI, gait speed, and handgrip strength in male patients( P<0.05 or P<0.001), and TIR was significantly positively associated with ASMI and gait speed in female patients( P<0.05 or P<0.01). After logistic regression adjusted for gender, age, body mass index, blood pressure, disease duration, HbA 1C, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein-choresterol, high density lipoprotein-choresterol, estimated glomerular filtration rate, protein intake, exercise intensity, smoking and alcohol consumption, an increase in TIR levels was associated with a decrease in the prevalence of severe sarcopenia( OR=0.923, 95% CI 0.878-0.970, P=0.002). The lowest quartile TIR significantly increased the risk of sarcopenia compared with the highest quartile TIR( OR=3.733, 95% CI 1.129-12.342, P=0.031). Conclusion:Decline in TIR is significantly associated with an increased risk of sarcopenia in older patients with type 2 diabetes.

Association of time in range with the severity of coronary artery disease in type 2 diabetic patients / 中华内分泌代谢杂志

Objective:To investigate the association of time in range(TIR) with the severity of coronary artery disease and acute coronary syndrome in patients with type 2 diabetes mellitus.Methods:A total of 216 patients with type 2 diabetes mellitus and coronary heart disease were recruited and undergone anthropometric and biochemical measurements, continuous glucose monitoring, and calculation of SYNTAX score. TIR was defined as the percentage of time within the glucose range of 3.9-10.0 mmol/L during 24 h. Spearman correlation analysis and multivariate linear regression analysis were used to evaluate the correlation factors of SYNTAX score. Multivariate logistic regression analysis was used to analyze the association of TIR with the severity of coronary artery disease and acute coronary syndrome. Results:Compared with patients with mild coronary artery disease, TIR in patients with moderate to severe coronary artery disease was lower[(69.4±17.3)% vs (60.8±17.8)%, t=3.0, P=0.003], and HbA 1C of patients with moderate to severe coronary artery disease was higher [(9.6±1.7)% vs (8.8±1.6)%, t=3.3, P=0.001]. SYNTAX score was negatively correlated with TIR ( r=-0.251, P<0.01) and positively correlated with HbA 1C ( r=0.249, P<0.01). Moreover, compared with HbA 1C (standardized coefficients=0.181, P=0.007), TIR (standardized coefficients=-0.192, P=0.004) had a greater influence on SYNTAX score. Multivariate linear regression analysis showed that TIR, HbA 1C, duration of diabetes and smoking were independently correlated with SYNTAX score. Multivariate logistic regression analysis revealed that compared with TIR Q1, Q3 and Q4 were independent protective factors for moderate to severe coronary artery disease (respectively, OR=0.61 and 0.59, 95% CI 0.39-0.96 and 0.38-0.94, P=0.014 and 0.009) and acute coronary syndrome (respectively, OR=0.51 and 0.39, 95% CI 0.32-0.95 and 0.26-0.75, P=0.022 and 0.008). Conclusion:TIR was significantly and independently correlated with the severity of coronary artery disease and acute coronary syndrome in type 2 diabetes mellitus after controlling confounding factors. When TIR level was decreased, the severity of coronary artery disease was aggravated, and SYNTAX score and the risk of acute coronary syndrome was increased.

Analysis of CYP17A1 gene variants in 5 patients with 17-hydroxylase deficiency / 中华医学遗传学杂志

Objective@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*Methods@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*Results@#Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation.@*Conclusion@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

Analysis of CYP17A1 gene variants in 5 patients with 17-hydroxylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*METHODS@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*RESULTS@#Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation.@*CONCLUSION@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

Analysis of clinical phenotypes and CYP21A2 gene variants in 18 patients with 21-hydroxylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genotype-phenotype correlation among 18 patients with 21-hydroxylase deficiency (21-OHD).@*METHODS@#PCR-Sanger sequencing was used to analyze the 10 exons and flanking regions of the CYP21A2 gene among the 18 patients and 20 healthy controls.@*RESULTS@#Seventeen patients had variants of the CYP21A2 gene. Eight patients (44.4%, 8/18) carried homozygous variants including p.Ile 173Asn (62.5%, 5/8), p.Pro31Leu (25.0%, 2/8), and IVS2-13A/C>G (12.5%, 1/8), respectively. Six patients (33.3%, 6/18) carried compound heterozygous variant, among which IVS2-13 A>G+p.Ile 173Asn were most common (50.0%). 94.4% (34/36) of the variant were pathogenic, with the most common variants being p.Ile173Asn (41.7%), IVS2-13A/C>G (19.4%), and p.Ile173Asn (7.5%). No variant was identified among the 20 healthy controls.@*CONCLUSION@#The majority of 21-OHD patients carried CYP21A2 gene variants in homozygous or compound heterozygous forms, among which the p.Ile173Asn was the most common one. There is a strong correlation between the genotypes and clinical phenotypes.

Approach to the patient with pancytopenia secondary to panhypopituitarism after craniopharyngioma surgery / 中华内分泌代谢杂志

Craniopharyngioma is the most common benign intracranial tumor in children. The major post-operative complication is dysfunction of pituitary, which can result in many complicate clinical manifestations with hormonal deficiencies. Normochromic anemia has been reported as a common hematologic abnormality. However, pancytopenia is rarely reported so far. Here we describe a 21-year-old inpatient with the main complaint of nasal bleeding, who accepted craniopharyngioma surgery 9 years ago. Laboratory tests showed pancytopenia secondary to panhypopituitarism. This paper aims to increasing the awareness of this disease and accumulating clinical experiences for the clinicians.

Study on the correlation between visfatin and mild cognitive impairment in elderly patients with diabetes / 中华老年医学杂志

Objective To explore the relationship between visfatin and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods A perspective study involving 75 hospitalized T2DM patients were divided into groups with(MCI,n=35)and without (NMCI,n =40)mild cognitive impairment.Another 30 non-diabetic patients were chosen as normal control(NC).Fasting plasma levels of glucose (FPG),insulin (FINS),lipid,glycosylated hemoglobin (HbAlc),HOMA-IR and visfatin were measured and calculated.Results The serum visfatin level was higher in MCI(28.81±3.32)μg/L than in NMCI(20.69±3.40)μg/L and NC(19.06±2.35)μg/L (F=96.491,P＜ 0.01).Visfatin was negatively correlated with Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) (r =-0.646,P ＜ 0.01),but positively correlated with course of disease,waist hip ratio,FPG,HbAlc,FINS,HOMA-IR and triglyceride (r=0.282,0.276,0.318,0.496,0.339,0.433,0.309,P＜0.05 or P＜0.01).MoCA-TS was negatively correlated with course of disease,HbAlc,HOMA-IR,triglyceride,total cholesterol,low density lipoprotein cholesterol (r =-0.582,-0.365,-0.234,-0.330,0.277,-0.238,P＜0.05 or P＜0.01),but positively correlated with high density lipoprotein cholesterol(r=0.290,P＜0.05).Higher values of visfatin(OR =3.246,P＜0.01),HbAlc(OR=2.308,P＜0.01)and course of disease(OR=1.634,P＜0.05)were the risk factors for MCI.Conclusions The elevated visfatin level might be a risk factor for MCI in T2DM patients.

The influence of blood glucose fluctuation on hippocampal tau protein phosphorylation of diabetic rats / 中华内分泌代谢杂志

Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.

The influence of blood glucose fluctuation on hippocampal tau protein phosphorylation of diabetic rats / 中华内分泌代谢杂志

Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.

Triglycerides and ratio of triglycerides to high-density lipoprotein cholesterol are better than liver enzymes to identify insulin resistance in urban middle-aged and older non-obese Chinese without diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Insulin resistance (IR) plays an important pathophysiological role in the development of diabetes, dyslipidemia, hypertension, and cardiovascular disease. Moreover, IR can occur even in non-obese people without diabetes. However, direct detection of IR is complicated. In order to find a simple surrogate marker of IR early in non-obese people, we investigate the association of commonly-used biochemical markers (liver enzymes and lipid profiles) with IR in urban middle-aged and older non-obese Chinese without diabetes.</p><p><b>METHODS</b>This cross-sectional study included 1 987 subjects (1 473 women). Fasting blood samples were collected for measurement of glucose, insulin, liver enzymes, lipid profiles and creatinine. Subjects whose homeostasis model of assessment-IR (HOMA-IR) index values exceeded the 75th percentile (2.67 for women and 2.48 for men) of the population were considered to have IR. The area under the receiver operating characteristic curve (ROC) was used to compare the power of potential markers in identifying IR.</p><p><b>RESULTS</b>Triglycerides (TG) and ratio of TG to high-density lipoprotein cholesterol (TG/HDL-C) discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic (ROC) curves (AUC) values were 0.770 (95% confidence interval 0.733-0.807) and 0.772 (0.736-0.809), respectively, for women and 0.754 (0.664-0.844) and 0.756 (0.672-0.840), respectively, for men. To identify IR, the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L (sensitivity 74.3%, specificity 71.0%) and 0.873 (sensitivity 70.1%, specificity 73.4%), respectively, for women, and 1.275 mmol/L (sensitivity 66.7%, specificity 74.4%) and 0.812 (sensitivity 75.8%, specificity 69.2%), respectively, for men.</p><p><b>CONCLUSION</b>TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.</p>