High Incidence of Diabetes Mellitus After Distal Pancreatectomy and Its Predictors

Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP (Distal Pancreatectomy); the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.

source: JCEM

Summary

A Long-term Follow-up Study

[Posted 26/Feb/2024]

AUDIENCE: Endocrinology, Nephrology

KEY FINDINGS: Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP; the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.

BACKGROUND: Aim of this study is to investigate the changes in diabetes-related traits before and after DP and to clarify the incidence of diabetes and its predictors.

DETAILS: Among 493 registered patients, 117 underwent DP. Among these, 56 patients without diabetes before surgery were included in the study. Glucose and endocrine function were prospectively assessed using a 75-g oral glucose tolerance test preoperatively, 1 month after DP, and every 6 months thereafter for up to 36 months. Pancreatic volumetry was performed using multidetector row computed tomography before and after surgery. Insulin secretion decreased and blood glucose levels worsened after DP. Residual pancreatic volume was significantly associated with the reserve capacity of insulin secretion but not with blood glucose levels or the development of diabetes. Among 56 patients, 33 developed diabetes mellitus. The cumulative incidence of diabetes at 36 months after DP was 74.1%. Multivariate Cox regression analysis showed that impaired glucose tolerance as a preoperative factor as well as a decreased insulinogenic index and impaired glucose tolerance at 1 month postoperatively were identified as risk factors for diabetes following DP.

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Copyright © The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.

Source: Imamura, S., Niwano. F., Babaya, N., et al. (2024). High Incidence of Diabetes Mellitus After Distal Pancreatectomy and Its Predictors: A Long-term Follow-up Study. The Journal of Clinical Endocrinology & Metabolism. 2024; 109(3): 619-630. Published: March, 2024. DOI: 10.1210/clinem/dgad634.



Associations of Biomarkers of Tubular Injury and Inflammation with Biopsy Features in Type 1 Diabetes

Biomarkers of tubular injury and inflammation were associated with kidney structural parameters in early type 1 diabetes and may be indicators of kidney disease risk.

source: Clin J Am Soc Nephrol.

Summary

[Posted 22/Jan/2024]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Biomarkers of tubular injury and inflammation were associated with kidney structural parameters in early type 1 diabetes and may be indicators of kidney disease risk.

BACKGROUND: Whether biomarkers of tubular injury and inflammation indicate subclinical structural kidney pathology early in type 1 diabetes remains unknown.

DETAILS: Authors investigated associations of biomarkers of tubular injury and inflammation with kidney structural features in 244 adults with type 1 diabetes from the Renin-Angiotensin System Study, a randomized, placebo-controlled trial testing effects of enalapril or losartan on changes in glomerular, tubulointerstitial, and vascular parameters from baseline to 5-year kidney biopsies. Biosamples at biopsy were assessed for kidney injury molecule 1 (KIM-1), soluble TNF receptor 1 (sTNFR1), arginine-to-citrulline ratio in plasma, and uromodulin and epidermal growth factor (EGF) in urine. We examined cross-sectional correlations between biomarkers and biopsy features and baseline biomarker associations with 5-year changes in biopsy features. Participants' mean age was 30 years (SD 10) and diabetes duration 11 years (SD 5); 53% were women. The mean GFR measured by iohexol disappearance was 128 ml/min per 1.73 m2 (SD 19) and median urinary albumin excretion was 5 μg/min (interquartile range, 3–8). KIM-1 was associated with most biopsy features: higher mesangial fractional volume (0.5% [95% confidence interval (CI), 0.1 to 0.9] greater per SD KIM-1), glomerular basement membrane (GBM) width (14.2 nm [95% CI, 6.5 to 22.0] thicker), cortical interstitial fractional volume (1.1% [95% CI, 0.6 to 1.6] greater), fractional volume of cortical atrophic tubules (0.6% [95% CI, 0.2 to 0.9] greater), and arteriolar hyalinosis index (0.03 [95% CI, 0.1 to 0.05] higher). sTNFR1 was associated with higher mesangial fractional volume (0.9% [95% CI, 0.5 to 1.3] greater) and GBM width (12.5 nm [95% CI, 4.5 to 20.5] thicker) and lower GBM surface density (0.003 μm2/μm3 [95% CI, 0.005 to 0.001] lesser). EGF and arginine-to-citrulline ratio correlated with severity of glomerular and tubulointerstitial features. Baseline sTNFR1, uromodulin, and EGF concentrations were associated with 5-year glomerular and tubulointerstitial feature progression.

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Copyright © American Society of Nephrology. All rights reserved.

Source: Limonte, C., Prince, D., Hoofnagle, A. N., et al. (2023). Associations of Biomarkers of Tubular Injury and Inflammation with Biopsy Features in Type 1 Diabetes. Clinical Journal of the American Society of Nephrology. 2024; 19(1): 44-55, January 2024. Published: January, 2024. DOI: 10.2215/CJN.0000000000000333.



Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity

Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

source: JCEM

Summary

[Posted 18/Jan/2024]

AUDIENCE: Endocrinology, Ophthalmology

KEY FINDINGS: Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

BACKGROUND: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials. Objective of the study was to present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.

DETAILS: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) <= 1 or no additional inflammation or progression in proptosis/diplopia for >=1 year, proptosis >=3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed. A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths.

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Copyright © The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.

Source: Douglas, R. S., Couch, S., Wester, S. T., et al. (2024). Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity. The Journal of Clinical Endocrinology & Metabolism. 2024; 109(1): 25-35. Published: January, 2024. DOI: 10.1210/clinem/dgad637.



Thyroid Function Tests in Children and Adolescents With Trisomy 21

By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

source: JCEM

Summary

Definition of Syndrome-Specific Reference Ranges.

[Posted 13/Nov/2023]

AUDIENCE: Endocrinology, Pediatric, Family Medicine

KEY FINDINGS: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

BACKGROUND: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. Aim of this study is to (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism.

DETAILS: In this retrospective, monocentric, observational analysis, authors included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. Authors determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15).

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Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.

Source: Cattoni, A., Molinari, S., Capitoli, G., et al. (2023). Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges. JCEM. 2023; 108(11): 2779-2788. Published: November, 2023. DOI: 10.1210/clinem/dgad333.



Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia

During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.

source: J Pediatr.

Summary

[Posted 26/Oct/2023]

AUDIENCE: Pediatric, Neurology, Family Medicine

KEY FINDINGS: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.

BACKGROUND: Objective of this study is to determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH).

DETAILS: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern.

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Copyright © Elsevier Inc. All rights reserved.

Source: Tetarbe, M., Wisnowski, J. L., Geyer, E., et al. (2023). Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia. J Pediatr.. Published: October, 2023. DOI: 10.1016/j.jpeds.2023.113560.



Refining the Definition of Stage 1 Type 1 Diabetes

The 15-year risk of progression to type 1 diabetes risk varies markedly from 18 to 88% based on the stringency of mIA definition. While initial categorization identifies highest-risk individuals, short-term follow-up over 2 years may help stratify evolving risk, especially for those with less stringent definitions of mIA.

source: Diabetes Care

Summary

An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity

[Posted 24/Oct/2023]

AUDIENCE: Endocrinology, Pediatric, Family Medicine

KEY FINDINGS: The 15-year risk of progression to type 1 diabetes risk varies markedly from 18 to 88% based on the stringency of mIA definition. While initial categorization identifies highest-risk individuals, short-term follow-up over 2 years may help stratify evolving risk, especially for those with less stringent definitions of mIA.

BACKGROUND: Aim of this study is to estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA).

DETAILS: Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S. who have an increased genetic risk for type 1 diabetes. Analysis included 16,709 infants-toddlers enrolled by age 2.5 years and comparison between groups using Kaplan-Meier survival analysis. Of 865 (5%) children with mIA, 537 (62%) progressed to type 1 diabetes. The 15-year cumulative incidence of diabetes varied from the most stringent definition (mIA/Persistent/2: two or more islet autoantibodies positive at the same visit with two or more antibodies persistent at next visit; 88% [95% CI 85-92%]) to the least stringent (mIA/Any: positivity for two islet autoantibodies without co-occurring positivity or persistence; 18% [5-40%]). Progression in mIA/Persistent/2 was significantly higher than all other groups (P < 0.0001). Intermediate stringency definitions showed intermediate risk and were significantly different than mIA/Any (P < 0.05); however, differences waned over the 2-year follow-up among those who did not subsequently reach higher stringency. Among mIA/Persistent/2 individuals with three autoantibodies, loss of one autoantibody by the 2-year follow-up was associated with accelerated progression. Age was significantly associated with time from seroconversion to mIA/Persistent/2 status and mIA to stage 3 type 1 diabetes.

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Copyright © American Diabetes Association. All rights reserved.

Source: Frohnert, B. I., Ghalwash, M., Li, Y., et al. (2023). Refining the Definition of Stage 1 Type 1 Diabetes: An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity. Diabetes Care . 2023; 46(10): 1753-1761. Published: October, 2023. DOI: 10.2337/dc22-1960.



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