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of glucose are necessary to capture short-term variability.

To investigate whether intermittently scanned continuous glucose monitoring (isCGM) significantly improves glycemic control compared with capillary self-monitored blood glucose (SMBG) in youth with type 1 diabetes and high-risk glycemic control.

This multicenter 6-month randomized, controlled, parallel-arm trial included 64 participants aged 13-20 years with established type 1 diabetes and glycated hemoglobin (HbA

) ≥9% (≥75 mmol/mol). Participants were allocated to 6-month intervention (isCGM; FreeStyle Libre; Abbott Diabetes Care, Witney, U.K.) (

= 33) or control (SMBG;

= 31) using minimization. KN-93 in vivo The primary outcome was the difference in change in HbA

from baseline to 6 months.

There was no evidence of a difference between groups for changes in HbA

at 6 months (adjusted mean 0.2% greater improvement for isCGM [95% CI -0.9 to 0.5] [-2.1 mmol/mol (95% CI -9.6 to 5.4)];

= 0.576). However, glucose-monitoring frequency was 2.83 (95% CI 1.72-4.65;

< 0.001) times higher in the isCGM group compared with that in the SMBG group at 6 months. The change in the Diabetes Treatment Satisfaction Questionnaire mean item score also favored isCGM at 6 months (

= 0.048), with no significant differences between groups for fear of hypoglycemia and quality of life (both general and diabetes specific) (all

> 0.1).

For youth with high-risk glycemic control, isCGM led to improvements in glucose testing frequency and diabetes treatment satisfaction. However, these did not translate to greater improvement in glycemic control over usual care with SMBG at 6 months.

For youth with high-risk glycemic control, isCGM led to improvements in glucose testing frequency and diabetes treatment satisfaction. However, these did not translate to greater improvement in glycemic control over usual care with SMBG at 6 months.

This epidemiological analysis of the pooled Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort describes the equivalence of a 1-percentage point increase in HbA

(such as from 7% to 8%) and years of additional age or duration of type 1 diabetes (T1D) relative to the risk of complications.

Separate Cox proportional hazards models determined the number of additional years of age and/or duration of T1D that would result in the same increase in risk of microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications and mortality as a 1-percentage point increase in HbA

.

The risk of any cardiovascular disease associated with a 1-percentage point increase in HbA

was equivalent to the risk associated with 4.3 (95% CI 2.7-5.9) additional years of age or 5.6 (95% CI 2.7-6.5) additional years' duration of T1D. The risk of estimated glomerular filtration rate <60 mL/min/1.73 m

and/or end-stage renal disease associated with a 1-percentage point increase in HbA

was equivalent to the risk associated with 12.1 (95% CI 8.3-15.9) additional years of age or 18.0 (95% CI 4.3-31.7) additional years' duration of T1D. The proliferative diabetic retinopathy risk associated with a 1-percentage point increase in HbA

was equivalent to the risk associated with 6.4 (95% CI 5.3-7.4) additional years' duration of T1D, while for mortality risk, it was equivalent to the risk associated with 12.9 (95% CI 6.6-19.3) additional years of age.

Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.

Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.

The risk genotype for the common variant rs7903146 of the transcription factor 7-like-2 (

) gene has been found to affect the incretin response in healthy and obese adults; however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the rs7903146 variant in the

gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, β-cell function relative to insulin sensitivity, the gastrointestinal-induced glucose disposal (GIGD) in obese youth with normal and impaired glucose tolerance.

Thirty-nine obese adolescents without diabetes (median age 15 [25th, 75th percentile 14, 18] years; BMI 37 [33, 43] kg/m

) were genotyped for the rs7903146 variant of

and underwent a 3-h oral glucose tolerance test (OGTT) followed by an isoglycemic intravenous glucose infusion (iso-intravenous glucose tolerance test [IVGTT]) to match the plasma glucose concent intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp.

A reduced incretin effect and its association with the

variant rs7903146 identify an early metabolic phenotype in obese youth without diabetes, featuring a higher plasma glucose peak at 1 h; lower insulin secretion, sensitivity, and clearance; and GIGD.

A reduced incretin effect and its association with the TCF7L2 variant rs7903146 identify an early metabolic phenotype in obese youth without diabetes, featuring a higher plasma glucose peak at 1 h; lower insulin secretion, sensitivity, and clearance; and GIGD.Naloxegol is a new peripherally acting mu-opioid receptor antagonist to treat opioid-induced constipation with supposedly no effect on opioid analgesia. We present a patient with cancer-related pain who developed acute opioid withdrawal symptoms due to an interaction between the opioid antagonist naloxone and naloxegol. He was treated with oxycodone sustained release because of poor pain control. For opioid-related constipation, he had been receiving naloxegol. He complained about worsening pain and constipation and oxycodone was switched to oxycodone/naloxone. Shortly after intake, he experienced acute severe agitation, anxiety, sweating, tachycardia, disorientation and yawning without improvement after intravenous midazolam. Only after intravenous morphine administration, symptoms were controlled. He was switched back to the previous oxycodone dose without naloxone, with naloxegol being maintained. In the light of this case we suggest to avoid the use of naloxone and naloxegol in combination, or at least, to use it with extreme caution and monitorisation of tolerance.