BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques...BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.展开更多
BACKGROUND Adrenal tuberculosis usually presents with bilateral involvement.It has special characteristics in computed tomography(CT)images,such as small size,low attenuation in the center,and peripheral rim enhanceme...BACKGROUND Adrenal tuberculosis usually presents with bilateral involvement.It has special characteristics in computed tomography(CT)images,such as small size,low attenuation in the center,and peripheral rim enhancement,which differ from those of primary tumors.CASE SUMMARY A 42-year-old female presented to the hospital with low back pain.She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever,fatigue,anorexia,night sweats,cough,or weight loss.Abdominal CT revealed an irregular 6.0 cm×4.5 cm mass with uneven density in the right adrenal gland,while the left adrenal gland was normal.No abnormalities were observed in plasma total cortisol(8 am),adrenocorticotropic hormone,aldosterone/renin ratio,blood catecholamines,or urine catecholamines.A fineneedle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis.After three years of anti-tuberculosis treatments,the large mass in the right adrenal gland was reduced to a slight enlargement.CONCLUSION This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor.Extended anti-tuberculosis therapy is recommended in such cases.展开更多
Mild thyroid stimulating hormone （TSH） elevations are highly prevalent whereas large proportion of individuals with TSH elevations is without chronic autoimmune thyroid diseases.TSH secretion exhibits a daily circad...Mild thyroid stimulating hormone （TSH） elevations are highly prevalent whereas large proportion of individuals with TSH elevations is without chronic autoimmune thyroid diseases.TSH secretion exhibits a daily circadian rhythm,and we previously reported that individuals with sleep disorders have significantly higher TSH levels than controls.展开更多
基金This retrospective analysis incorporated data from two clinical trials(CTR20220854 and CTR20222843)sponsored by Chongqing Chenan Biopharmaceutical Co.,Ltd.and Jiangsu Hengrui Pharmaceuticals Co.,Ltd.However,these sponsors did not partake in the study design,data interpretation,or manuscript preparation.
文摘BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.
文摘BACKGROUND Adrenal tuberculosis usually presents with bilateral involvement.It has special characteristics in computed tomography(CT)images,such as small size,low attenuation in the center,and peripheral rim enhancement,which differ from those of primary tumors.CASE SUMMARY A 42-year-old female presented to the hospital with low back pain.She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever,fatigue,anorexia,night sweats,cough,or weight loss.Abdominal CT revealed an irregular 6.0 cm×4.5 cm mass with uneven density in the right adrenal gland,while the left adrenal gland was normal.No abnormalities were observed in plasma total cortisol(8 am),adrenocorticotropic hormone,aldosterone/renin ratio,blood catecholamines,or urine catecholamines.A fineneedle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis.After three years of anti-tuberculosis treatments,the large mass in the right adrenal gland was reduced to a slight enlargement.CONCLUSION This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor.Extended anti-tuberculosis therapy is recommended in such cases.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81600603）.
文摘Mild thyroid stimulating hormone （TSH） elevations are highly prevalent whereas large proportion of individuals with TSH elevations is without chronic autoimmune thyroid diseases.TSH secretion exhibits a daily circadian rhythm,and we previously reported that individuals with sleep disorders have significantly higher TSH levels than controls.
