Journal of Clinical and Translational Endocrinology最新文献

Aims

Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes.

Methods

We retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV₁, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes.

Results

Age was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m² (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m² (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV₁ improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013).

Conclusion

Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV₁. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.

Background

Cystic fibrosis related diabetes (CFRD) is associated with insulin-remediable pulmonary decline, so early detection is critical. Continuous glucose monitors (CGM) have shown promise in screening but are not recommended by clinical practice guidelines. Little is known about the reproducibility of CGM results for a given patient.

Methods

Twenty non-insulin treated adults and adolescents with CF placed an in-home CGM and wore it for two 14-day periods. Participants underwent a mixed meal tolerance test (MMTT) on day 5 of each 14-day period. Glycemic data from CGM 1 and CGM 2 were compared regarding published thresholds to define abnormality: percent time >140 mg/dL of ≥4.5%, percent time >140 mg/dL of >17.5%, and percent time >180 mg/dL of >3.4%. Results of the repeat MMTT were compared for peak glucose and 2-hour glucose thresholds: >140 mg/dL, >180 mg/dL, and >200 mg/dL.

Results

For percent time >140 mg/dL of ≥ 4.5%, five of 20 subjects had conflicting results between CGM 1 and CGM 2. For percent time >140 mg/dL of >17.5% and >180 mg/dL of >3.4%, only one of 20 subjects had conflicting results between CGM 1 and CGM 2. On the MMTT, few participants had a 2-hour glucose >140 mg/dL. Peak glucose >140 mg/dL, 180 mg/dL, and 200 mg/dL were more common, with 10–37% of participants demonstrating disagreement between CGM 1 and CGM 2.

Conclusions

Repeated in-home CGM acquisitions show reasonable reproducibility regarding the more stringent thresholds for time >140 mg/dL and >180 mg/dL. More data is needed to determine thresholds for abnormal mixed meal tolerance tests in CFRD screening.

Objective

Pancreatic neuroendocrine tumors (PNETs) are rare, but their incidence has risen significantly in recent years. Whereas diabetes mellitus (DM) is recognized in association with chronic pancreatitis and pancreatic cancer, it has not been well-characterized concerning non-functioning (NF)-PNETs.

Study aim: to determine whether NF-PNETs are associated with DM/ Pre-DM and characterize the features of this putative association.

Methods

Retrospective study to evaluate rate of Pre-DM /DM in subjects with NF-PNETs.

Results

Study cohort of 129 patients with histologically confirmed NF-PNETs, ∼60% were men (M/F: 77/52). Abnormal glucose metabolism that preceded any treatment was seen in 70% of this cohort: overt DM in 34% and Pre-DM in 36% of the subjects. However, during follow-up, the overall prevalence rose to 80.6%, owing exclusively to newly diagnosed DM in subjects who received treatment.

Patients with DM/Pre-DM were older (65 ± 11; 54 ± 14; p < 0.0001), the tumor was more commonly localized in the pancreatic body and tail (76.5% vs. 23.5% p = 0.03), while BMI (27 ± 6 vs. 28 ± 5 kg/m2), and tumor size (2.4 ± 2 vs. 2.9 ± 3.2 cm) were similar. The relative prevalence of DM in our cohort of NF-PNETs was 1.6 higher than that in the age and gender-adjusted general Israeli population (95 %CI: 1.197–2.212p = 0.03).

Conclusions

We found a high rate of impaired glucose metabolism, either DM or Pre-DM, in a large cohort of NF-PNETs. The high prevalence of diabetes/pre-diabetes was unrelated to obesity or tumor size. This observation should increase awareness of the presence of DM on presentation or during treatment of “NF”-PNETs.

Purpose

Primary hyperparathyroidism (PHPT) is the underlying etiology for 90% of patients with hypercalcemia. PHPT patients have traditionally been characterized as being symptomatic or asymptomatic. However, we submit that even “asymptomatic” patients may still have clinical features, posing the idea of coining asymptomatic disease as a misnomer. This paper presents a systematic review and meta-analysis elucidating the differences between asymptomatic and symptomatic PHPT in the literature.

Methods

A comprehensive literature search was conducted in PubMed, Cochrane, and Web of Science databases for articles published from 2012 to 2022. Inclusion criteria consisted of all studies comparing symptomatic and asymptomatic PHPT patients. Two reviewers independently evaluated the literature using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The level of evidence was determined using the Oxford Center for Level of Evidence-Based Medicine. Data were extracted, and a meta-analysis was performed. I² index was employed for heterogeneity.

Results

There were 18 studies included, with a total of 4238 patients. The average age of patients included was 56.37, with 25.7% of the cohort being male. Several studies reported clinical features even for the “asymptomatic” group. Patients in the symptomatic group tended to have higher levels of PTH and calcium. The asymptomatic group had greater levels of vitamin D. There was observed heterogeneity between the studies.

Conclusions

More extreme PTH, calcium values, and low vitamin D levels were seen in patients with symptomatic disease. However, asymptomatic patients occasionally exhibited clinical features. Therefore, the terminology of “asymptomatic” disease is likely inappropriate for these patients.

Aims

Hybrid closed loop (HCL) insulin delivery systems improve glycemia and quality of life among youth with type 1 diabetes (T1D), however there are inequities in use. We aimed to evaluate whether differences in positive expectancy of HCL systems may explain differences in use.

Methods

Fifteen publicly-insured, non-Hispanic Black (NHB) youth with hemoglobin A1_C (HbA1c) ≥ 10% enrolled in a study exploring changes in glycemia and person reported outcomes (PRO) during 6 months of Tandem t:slim X2 insulin pump with Control-IQ technology. At baseline youth and parents completed PROs, including Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations (INSPIRE) survey assessing positive expectancy of HCL use, and Problem Areas in Diabetes (PAID) survey assessing diabetes-related distress. Differences between this cohort and the Tandem Control-IQ pediatric pivotal trial (DCLP5) cohort were assessed.

Results

As compared to the DCLP5 cohort (0% NHB, 10% publicly-insured), baseline glycemic indicators were suboptimal (M_HbA1c 11.9 ± 1.4% vs 7.6 ± 0.9%, p < 0.0001; continuous glucose monitor (CGM) time-above-range > 180 mg/dL 82 ± 15% vs 45 ± 18%, p < 0.0001). INSPIRE scores in both cohorts were equally high among youth (80 ± 10 vs 77 ± 13, p = 0.41) and parents (88 ± 14 vs 85 ± 11, p = 0.37). PAID scores were higher among parents (68 ± 19 vs 43 ± 16, p < 0.0001), but not youth (43 ± 16 vs 35 ± 16, p = 0.09) in the historically marginalized cohort as compared to the DCLP5 cohort.

Conclusions

Despite differences in glycemic control and diabetes related burden, positive expectancy of HCL systems is comparable among historically marginalized youth with T1D and the predominantly non-Hispanic White, privately insured DCLP5 cohort. These findings suggest that differences in perceptions of HCL technology may not explain inequities in use.

Background

The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and type 2 diabetes mellitus (T2D) and its cardiovascular outcomes have not been sufficiently studied.

Methods

2,986 adults with T2D from the Joslin Diabetes Center at Upstate Medical University were assessed for ADHD-like symptoms, executive dysfunction, and emotional control using the Adult Self-Report Scale V1.1 (ASRS) expanded version. Surveys were sent electronically, and clinical data were obtained from the electronic medical record. Pearson chi-square test was used for categorical variables association. When ASRS scores were the dependent variable, negative binomial regression correcting for demographic variables that were associated with the ASRS scores was used.

Results

155 (49.2%) of respondents met DSM-5 criteria for ADHD using the ASRS scores; Only ten (3.6%) of respondents had an ICD10 diagnosis of ADHD in their medical record; Forty-three (13.7%) had either a diagnosis of ADHD in the medical history or were taking medications used by people with ADHD. Higher levels of ADHD-like symptoms were found in patients with T2D compared with population norms. There was a modest association of the ASRS executive dysfunction subscale with overall cardiovascular comorbidities (p = 0.03). However, the p-value did not survive the multiple testing correction. Both ADHD-like symptoms and symptoms associated with emotional control, however, were not associated with specific cardiovascular diseases, hypertension, or with HbA1c, LDL-cholesterol, triglycerides, ALT, creatinine, or eGFR.

Conclusion

Our results suggest that adults with T2D attending a tertiary care diabetes clinic are at risk for having ADHD-like symptoms, highlighting the importance of screening for ADHD symptoms in this specialty setting and referring undiagnosed adult patients for further assessment and treatment of ADHD. Larger studies are needed to clarify the relationship between ADHD-like symptoms, executive dysfunction, and emotional control with diabetic control and comorbidities.

Aims

To risk-stratify patients with type 2 diabetes mellitus (T2DM) according to the IDF-DAR 2021 guidelines and observe their responsiveness to risk-category-based recommendations and fasting experience.

Methods

This prospective study, conducted in the peri-Ramadan period of 2022, evaluated adults with T2DM and categorized them using the IDF-DAR 2021 risk stratification tool. Recommendations for fasting according to the risk categories were made, their intention to fast was recorded, and follow-up data were collected within one month of the end of Ramadan.

Results

Among 1328 participants (age 51.1 ± 11.9 years, female 61.1 %), only 29.6 % had pre-Ramadan HbA1c < 7.5 %. According to the IDF-DAR risk category, the frequencies of participants in the low-risk (should be able to fast), moderate-risk (not to fast), and high-risk (should not fast) groups were 44.2 %, 45.7 %, and 10.1 %, respectively. Most (95.5 %) intended to fast, and 71 % fasted the full 30 days of Ramadan. The overall frequencies of hypoglycemia (3.5 %) and hyperglycemia (2.0 %) were low. Hypoglycemia and hyperglycemia risks were 3.74-fold and 3.86-fold higher in the high-risk group than in the low-risk group.

Conclusion

The new IDF-DAR risk scoring system seems conservative in the risk categorization of T2DM patients in terms of fasting complications.

Background

Hypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak.

Methods

Retrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women.

Results

Statistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c.

Conclusion

In the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

Objectives

Type 1 diabetes (T1D) is highly prevalent in Somali immigrant children and hemoglobin A1c (HbA1c) levels are elevated in this population compared to non-Hispanic Whites. Current self-management diabetes education has not been tailored to this population. We aimed to improve delivery of T1D education to Somali immigrants by developing and testing a culturally-appropriate video-based curriculum.

Methods

This cross-sectional study involved Somali youth ≤ 19 years with T1D followed at two pediatric tertiary centers in Minnesota. Ten Somali-language T1D education videos were developed (∼60 min for total program) based on core ADA curriculum and tailored to address cultural concerns and misconceptions. A diabetes knowledge questionnaire was administered to parents of all participants and to children aged ≥12 years. Pre- and post-educational session questionnaire mean scores were compared using a paired t-test to assess knowledge improvement immediately post-video education (primary endpoint) and retention at 3 months (secondary endpoint). HbA1c was measured pre- and 6 months post education (exploratory endpoint).

Results

Twenty-two Somali parents of 22 children participated (mean age 12.3 ± 4 years; 36 % female), 12 children ≥12 years. Diabetes knowledge scores significantly improved immediately post-video education compared to baseline (p = 0.012). This improvement persisted 3 months later (p = 0.0008). There was no significant change in mean HbA1c from baseline at 6 months post education (9.0 ± 1.5 % vs 9.3 ± 1.9; p = 0.6).

Conclusion

Culturally and linguistically tailoring diabetes education materials to African immigrants and delivering it audio-visually could improve effectiveness of diabetes education and increase knowledge and retention compared to simply translating standard diabetes education materials. The effect on HbA1c needs further study with a larger sample size.

Background

Studies in adults indicate that macronutrient ingestion yields an acute anti-resorptive effect on bone, reflected by decreases in C-terminal telopeptide (CTX), a biomarker of bone resorption, and that gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), facilitate this response. There remain knowledge gaps relating to other biomarkers of bone turnover, and whether gut-bone cross-talk is operative during the years surrounding peak bone strength attainment. This study first, describes changes in bone resorption during oral glucose tolerance testing (OGTT), and second, tests relationships between changes in incretins and bone biomarkers during OGTT and bone micro-structure.

Methods

We conducted a cross-sectional study in 10 healthy emerging adults ages 18–25 years. During a multi-sample 2-hour 75 g OGTT, glucose, insulin, GIP, GLP-1, CTX, bone-specific alkaline phosphatase (BSAP), osteocalcin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL), sclerostin, and parathyroid hormone (PTH) were assayed at mins 0, 30, 60, and 120. Incremental areas under the curve (iAUC) were computed from mins 0–30 and mins 0–120. Tibia bone micro-structure was assessed using second generation high resolution peripheral quantitative computed tomography.

Results

During OGTT, glucose, insulin, GIP, and GLP-1 increased significantly. CTX at min 30, 60, and 120 was significantly lower than min 0, with a maximum decrease of about 53 % by min 120. Glucose-iAUC_0-30 inversely correlated with CTX-iAUC_0-120 (rho = -0.91, P < 0.001), and GLP-1-iAUC_0-30 positively correlated with BSAP-iAUC_0-120 (rho = 0.83, P = 0.005), RANKL-iAUC_0-120 (rho = 0.86, P = 0.007), and cortical volumetric bone mineral density (rho = 0.93, P < 0.001).

Conclusions

Glucose ingestion yields an anti-resorptive effect on bone metabolism during the years surrounding peak bone strength. Cross-talk between the gut and bone during this pivotal life stage requires further attention.