Priya Prahalad, MD

Abstract

Previous studies have suggested that clear HbA1c target setting by the diabetes team is associated with HbA1c outcomes in adolescents. The aim of this study was to evaluate whether this finding is consistent in a larger cohort of children from centers participating in the SWEET international diabetes registry. A questionnaire was sent out to 76 SWEET centers, of which responses from 53 pediatric centers were included (70%). Descriptive outcomes were presented as median with lower and upper quartile. The association between the centers' target HbA1c and mean outcome HbA1c was calculated using linear regression adjusted for age, diabetes duration, sex, and gross domestic product. Median age of the children in the studied centers (n = 35,483) was 13.3 [12.6-14.6] years (49% female). Of the 53 centers, 13.2% reported an HbA1c target between 6.0 and 6.5%, 32.1% had a target between 6.0 and 7.0%, 18.9% between 7.0 and 7.5%, and 3.8% between 7.5 and 8.5%. No specific target value was reported by 32.1% of all centers. Median HbA1c across all centers was 7.9 [7.6-8.3] %. Adjusted regression analysis showed a positive association between HbA1c outcome and target HbA1c (p = 0.005).Conclusions: This international study demonstrated that a lower target for HbA1c was associated with better metabolic control. It is unclear whether low target values result in better metabolic control, or lower HbA1c values actually result in more ambitious target values. This target setting could contribute to the differences in HbA1c values between centers and could be an approach for improving metabolic outcomes. What is Known: Target setting of HbA1c is important in children and adolescents with type 1 diabetes. The optimal therapeutic approach of children with type 1 diabetes requires a trained multidisciplinary team. What is New: Lower HbA1c targets are associated with better metabolic control. No associations between the composition of the diabetes teams and metabolic control could be demonstrated.

View details for DOI 10.1007/s00431-020-03891-2

View details for PubMedID 33415466

Abstract

OBJECTIVES: To describe clinical presentation and long-term outcomes in a large cohort of children diagnosed with thiamine-responsive megaloblastic anemia (TRMA)-related diabetes.METHODS: Data from the Diabetes Patienten Verlaufsdokumentation (DPV) and Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference (SWEET) registries were used to identify cases. Complementary information was collected through a chart review of each case. Descriptive analyses with medians and interquartile ranges and numbers (proportions) were tabulated.RESULTS: We identified 23 cases (52% male) in the 2 registries. Eighteen (78%) had genetic confirmation of TRMA. Median age at diabetes onset was 1.4 (quartiles 0.8 to 3.6) years and median age at initiation of thiamine treatment was 5.9 (2.4 to 12.4) years. At their most recent visit, patients' median age was 14.3 (8.1 to 17.5) years, glycated hemoglobin level was 6.9% (6.1% to 7.9%), insulin dose was 0.9 (0.4 to 1.2) units/kg per day and thiamine dose was 200 (100 to 300) mg/day. Three patients were not treated with insulin or antidiabetic drugs. There was no difference in diabetes outcomes in patients with initiation of thiamine 1 year after diabetes onset compared to patients with initiation of thiamine >1 year after diabetes onset.CONCLUSIONS: This is the longest case series of pediatric TRMA-related diabetes reported to date. Diabetes onset often occurs several years before initiation of thiamine supplementation. Early initiation of thiamine (within 1 year of diabetes onset) was not linked to improved diabetes outcome. However, the role of thiamine in pancreatic function needs further assessment. Patients with TRMA-related diabetes maintained good glycemic control even after 9 years (median) of follow up.

View details for DOI 10.1016/j.jcjd.2020.11.006

View details for PubMedID 33388275

Abstract

INTRODUCTION: Population-level and individual-level analyses have strengths and limitations as do 'blackbox' machine learning (ML) and traditional, interpretable models. Diabetes mellitus (DM) is a leading cause of morbidity and mortality with complex sociodemographic dynamics that have not been analyzed in a way that leverages population-level and individual-level data as well as traditional epidemiological and ML models. We analyzed complementary individual-level and county-level datasets with both regression and ML methods to study the association between sociodemographic factors and DM.RESEARCH DESIGN AND METHODS: County-level DM prevalence, demographics, and socioeconomic status (SES) factors were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings and merged with US Census data. Analogous individual-level data were extracted from 2007 to 2016 National Health and Nutrition Examination Survey studies and corrected for oversampling with survey weights. We used multivariate linear (logistic) regression and ML regression (classification) models for county (individual) data. Regression and ML models were compared using measures of explained variation (area under the receiver operating characteristic curve (AUC) and R2).RESULTS: Among the 3138 counties assessed, the mean DM prevalence was 11.4% (range: 3.0%-21.1%). Among the 12824 individuals assessed, 1688 met DM criteria (13.2% unweighted; 10.2% weighted). Age, gender, race/ethnicity, income, and education were associated with DM at the county and individual levels. Higher county Hispanic ethnic density was negatively associated with county DM prevalence, while Hispanic ethnicity was positively associated with individual DM. ML outperformed regression in both datasets (mean R2 of 0.679 vs 0.610, respectively (p<0.001) for county-level data; mean AUC of 0.737 vs 0.727 (p<0.0427) for individual-level data).CONCLUSIONS: Hispanic individuals are at higher risk of DM, while counties with larger Hispanic populations have lower DM prevalence. Analyses of population-level and individual-level data with multiple methods may afford more confidence in results and identify areas for further study.

View details for DOI 10.1136/bmjdrc-2020-001725

View details for PubMedID 33229378

View details for DOI 10.2337/db20-1801-P

View details for Web of Science ID 000554509804067

View details for DOI 10.2337/db20-1289-P

View details for Web of Science ID 000554509803063

View details for DOI 10.2337/db20-1185-P

View details for Web of Science ID 000554509802428

View details for DOI 10.2337/db20-159-LB

View details for Web of Science ID 000554509800310

View details for DOI 10.2337/db20-1295-P

View details for Web of Science ID 000554509803069

View details for DOI 10.2337/db20-1297-P

View details for Web of Science ID 000554509803071

View details for DOI 10.2337/db20-1294-P

View details for Web of Science ID 000554509803068

View details for Web of Science ID 000514025300046

View details for Web of Science ID 000514025300602

View details for DOI 10.2337/dc19-1214

View details for PubMedID 31672703

View details for DOI 10.1111/pedi.12832

View details for Web of Science ID 000468283100001

Abstract

Background Neonatal severe hyperparathyroidism (NSHPT) is commonly treated with either parathyroidectomy or pharmacologic agents with varying efficacy and numerous side effects. Reports of using cinacalcet for NSHPT have increased, however, the effective dose for pediatric patients from the onset of symptoms through infancy has not been established. Case presentation We describe the clinical course of a newborn with a de novo R185Q mutation in the calcium-sensing receptor (CASR) gene, causing NSHPT. The infant received cinacalcet from the first days of life until 1 year of age. Conclusions Cinacalcet therapy effectively controlled the patient's serum calcium, phosphorus, and parathyroid hormone (PTH) levels without side effects.

View details for PubMedID 30730839

Abstract

Diabetes Technology Society (DTS) convened a meeting about the US Food and Drug Administration (FDA) Digital Health Software Precertification Program on August 28, 2018. Forty-eight attendees participated from clinical and academic endocrinology (both adult and pediatric), nursing, behavioral health, engineering, and law, as well as representatives of FDA, National Institutes of Health (NIH), National Telecommunications and Information Administration (NTIA), and industry. The meeting was intended to provide ideas to FDA about their plan to launch a Digital Health Software Precertification Program. Attendees discussed the four components of the plan: (1) excellence appraisal and certification, (2) review pathway determination, (3) streamlined premarket review process, and (4) real-world performance. The format included (1) introductory remarks, (2) a program overview presentation from FDA, (3) roundtable working sessions focused on each of the Software Precertification Program's four components, (4) presentations reflecting the discussions, (5) questions to and answers from FDA, and (6) concluding remarks. The meeting provided useful information to the diabetes technology community and thoughtful feedback to FDA.

View details for PubMedID 30394807

View details for PubMedID 30020810

Abstract

With the evolution of diabetes technology, those living with Type 1 diabetes are given a wider arsenal of tools with which to achieve glycaemic control and improve patient-reported outcomes. Furthermore, the use of these technologies may help reduce the risk of acute complications, such as severe hypoglycaemia and diabetic ketoacidosis, as well as long-term macro- and microvascular complications. In addition, diabetes technology can have a beneficial impact on psychosocial health by reducing the burden of diabetes. Unfortunately, diabetes goals are often unmet and people with Type 1 diabetes too frequently experience acute and long-term complications of this condition, in addition to often having less than ideal psychosocial outcomes. Increasing realization of the importance of patient-reported outcomes is leading to diabetes care delivery becoming more patient-centred. Diabetes technology in the form of medical devices, digital health and big data analytics have the potential to improve clinical care and psychosocial support, resulting in lower rates of acute and chronic complications, decreased burden of diabetes care, and improved quality of life. This article is protected by copyright. All rights reserved.

View details for PubMedID 29356074

Abstract

This article reviews mobile medical applications that are commercially available in the United States or European Union (EU) and are (1) associated with published data of clinical outcomes in the peer-reviewed literature during the past 5 years, (2) cleared by the US Food and Drug Administration (FDA) in the United States, or (3) a recipient of a CE (Conformit Europenne) mark by the EU. Many of these applications have been shown to positively affect outcomes in the short term, but long-term studies are needed. Until more data are available, consumers and professionals can consider guidance based on FDA/CE status.

View details for DOI 10.1016/j.ecl.2016.06.001

View details for PubMedID 27823614

Abstract

Cleared blood glucose monitor (BGM) systems do not always perform as accurately for users as they did to become cleared. We performed a literature review of recent publications between 2010 and 2014 that present data about the frequency of inaccurate performance using ISO 15197 2003 and ISO 15197 2013 as target standards. We performed an additional literature review of publications that present data about the clinical and economic risks of inaccurate BGMs for making treatment decisions or calibrating continuous glucose monitors (CGMs). We found 11 publications describing performance of 98 unique BGM systems. 53 of these 98 (54%) systems met ISO 15197 2003 and 31 of the 98 (32%) tested systems met ISO 15197 2013 analytical accuracy standards in all studies in which they were evaluated. Of the tested systems, 33 were identified by us as FDA-cleared. Among these FDA-cleared BGM systems, 24 out of 32 (75%) met ISO 15197 2003 and 15 out of 31 (48.3%) met ISO 15197 2013 in all studies in which they were evaluated. Among the non-FDA-cleared BGM systems, 29 of 65 (45%) met ISO 15197 2003 and 15 out of 65 (23%) met ISO 15197 2013 in all studies in which they were evaluated. It is more likely that an FDA-cleared BGM system, compared to a non-FDA-cleared BGM system, will perform according to ISO 15197 2003 ((2) = 6.2, df = 3, P = 0.04) and ISO 15197 2013 ((2) = 11.4, df = 3, P = 0.003). We identified 7 articles about clinical risks and 3 articles about economic risks of inaccurate BGMs. We conclude that a significant proportion of cleared BGMs do not perform at the level for which they were cleared or according to international standards of accuracy. Such poor performance leads to adverse clinical and economic consequences.

View details for DOI 10.1177/1932296815584797

View details for PubMedID 25990294

Abstract

Tumor development, growth, and metastasis depend on the provision of an adequate vascular supply. This can be due to regulated angiogenesis, recruitment of circulating endothelial progenitors, and/or vascular transdifferentiation. Our previous studies showed that retinoic acid (RA) treatment converts a subset of breast cancer cells into cells with significant endothelial genotypic and phenotypic elements including marked induction of VE-cadherin, which was responsible for some but not all morphological changes. The present study demonstrates that of the endothelial-related genes induced by RA treatment, only a few were affected by knockdown of VE-cadherin, ruling it out as a regulator of the RA-induced endothelial genotypic switch. In contrast, knockdown of the RA-induced gene COUP-TFII prevented the formation of networks in Matrigel but had no effect on VE-cadherin induction or cell fusion. Two pan-kinase inhibitors markedly blocked RA-induced VE-cadherin expression and cell fusion. However, RA treatment resulted in a marked and broad reduction in tyrosine kinase activity. Several genes in the TGFbeta signaling pathway were induced by RA, and specific inhibition of the TGFbeta type I receptor blocked both RA-induced VE-cadherin expression and cell fusion. Together these data indicate a role for the TGFbeta pathway and COUP-TFII in mediating the endothelial transdifferentiating properties of RA.

View details for DOI 10.1371/journal.pone.0010023

View details for PubMedID 20386594

Abstract

Many aspects of development, tumor growth and metastasis depend upon the provision of an adequate vasculature. This can be a result of regulated angiogenesis, recruitment of circulating endothelial progenitors and/or vascular trans-differentiation. The present study demonstrates that treatment of SKBR-3 breast cancer cells with retinoic acid (RA), an important regulator of embryogenesis, cancer and other diseases, stimulates the formation of networks in Matrigel. RA-treatment of SKBR-3 cells co-cultured with human umbilical vein endothelial cells resulted in the formation of mixed structures. RA induces expression of many endothelial genes including vascular endothelial (VE) cadherin. VE-cadherin was also induced by RA in a number of other breast cancer cells. We show that RA-induced VE-cadherin is responsible for the RA-induced morphological changes. RA rapidly induced the expression of Sox-9 and ER81, which in turn form a complex on the VE-cadherin promoter and are required to mediate the transcriptional regulation of VE-cadherin by RA. These data indicate that RA may promote the expression of endothelial genes resulting in endothelial-like differentiation, or provide a mechanism whereby circulating endothelial progenitor cells could be incorporated into a growing organ or tumor.

View details for DOI 10.1371/journal.pone.0002714

View details for Web of Science ID 000264057200057

View details for PubMedID 18628953

Abstract

The attachment of epithelial cells to the extracellular matrix substratum is essential for their differentiation and polarization. Despite this, the precise adhesion mechanism and its regulation are poorly understood. In the kidney, an ischemic insult causes renal tubular epithelial cells to detach from the basement membrane, even though they remain viable. To understand this phenomenon, and to probe the regulation of epithelial cell attachment, we used a model system consisting of newly adherent Madin-Darby canine kidney (MDCK) cells subjected to ATP depletion to mimic ischemic injury. We found that MDCK cells detach from collagen I after 60 min of ATP depletion but reattach when resupplied with glucose. Detachment is not caused by degradation or endocytosis of beta(1)-integrins, which mediate attachment to collagen I. Basal actin filaments and paxillin-containing adhesion complexes are disrupted by ATP depletion and quickly reform on glucose repletion. However, partial preservation of basal actin by overexpression of constitutively active RhoA does not significantly affect cell detachment. Furthermore, Y-27632, an inhibitor of the RhoA effector Rho-kinase, does not prevent reattachment of cells on glucose addition, even though reformation of central stress fibers and large adhesion complexes is blocked. In contrast, reattachment of ATP-depleted cells and detachment of cells not previously subjected to ATP depletion are prevented by ML-7, an inhibitor of myosin light chain kinase (MLCK). We conclude that initial adherence of MDCK cells to a collagen I substratum is mediated by peripheral actin filaments and adhesion complexes regulated by MLCK but not by stress fibers and adhesion complexes controlled by RhoA.

View details for DOI 10.1152/ajpcell.00124.2003

View details for Web of Science ID 000188707600027

View details for PubMedID 14644769