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Partial Clinical Remission Of Type 1 Diabetes Mellitus In Children: Clinical Applications And Challenges With Its Definitions, Benjamin U. Nwosu

Benjamin U. Nwosu

The honeymoon phase, or partial clinical remission (PCR) phase, of Type 1 diabetes mellitus (T1DM) is a transitory period that is marked by endogenous insulin production by surviving β cells following a diabetes diagnosis and the introduction of insulin therapy. It is a critical window in the course of the disease that has short and long-term implications for the patient, such as a significant reduction in the risk of long-term complications of T1DM. To promote long-term cardiovascular health in children with newly diagnosed T1DM, three key steps are necessary: the generation of a predictive model for non-remission, the adoption of …

Pubertal Lipid Levels Are Significantly Lower In Youth With Type 1 Diabetes Who Experienced Partial Clinical Remission, Benjamin U. Nwosu, Shwetha Rupendu, Emily Zitek-Morrison, Deepa Patel, Tony R. Villalobos-Ortiz, Gabrielle Jasmin, Bruce A. Barton

Benjamin U. Nwosu

Importance: The physiologic changes in lipids during puberty in type 1 diabetes (T1D) is unclear as subjects in previous studies were not stratified by partial clinical remission (PCR) status.

Aim: To determine the effect of PCR on lipid changes during puberty in youth with T1D.

Subjects and Methods: A retrospective cross-sectional study of 194 subjects consisting of 71 controls of age 12.9±1.3y and 123 subjects with T1D stratified into remitters (n=44, age 13.0±0.8y) and non-remitters (n=79, age 11.2±0.6y). PCR was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging.

Results: Among the pubertal cohort, low-density …

Tobacco Smoke Exposure Is An Independent Predictor Of Vitamin D Deficiency In Us Children, Benjamin U. Nwosu, Philip Kum-Nji

Benjamin U. Nwosu

IMPORTANCE: The role of tobacco-smoke exposure on serum vitamin D concentration in US pediatric population is not known. We hypothesized that tobacco smoke exposure would increase the prevalence of vitamin D deficiency in US children.

METHODS: Representative national data were accessed from the National Health and Nutrition Examination Survey (NHANES) 2009-2010 databank on 2,263 subjects of ages 3 to 17 years. Subjects were categorized into two groups based on their age: children, if <10 >years; and youth if 10 to 17 years. Descriptive and multiple logistic regression analyses were conducted to determine the effect of serum cotinine-verified tobacco smoke exposure on …

Children With Type 1 Diabetes Who Experienced A Honeymoon Phase Had Significantly Lower Ldl Cholesterol 5 Years After Diagnosis, Benjamin U. Nwosu, Bo Zhang, Sanaa S. Ayyoub, Stephanie Choi, Tony R. Villalobos-Ortiz, Laura C. Alonso, Bruce A. Barton

Benjamin U. Nwosu

IMPORTANCE: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized.

AIM: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status.

SUBJECTS AND METHODS: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 +/- 2.9 years, [male 11.7 +/- 2.9 years, (n = 55); female 12.0 +/- …

Partial Clinical Remission In Type 1 Diabetes: A Comparison Of The Accuracy Of Total Daily Dose Of Insulin Of <0.3 Units/Kg/Day To The Gold Standard Insulin-Dose Adjusted Hemoglobin A1c Of ≤9 For The Detection Of Partial Clinical Remission, Rachel L. Lundberg, Katherine R. Marino, Aastha Jasrotia, Louise S. Maranda, Bruce A. Barton, Laura C. Alonso, Benjamin U. Nwosu

Benjamin U. Nwosu

BACKGROUND: It is unclear whether the gold standard test for the detection of partial clinical remission (PCR) in new-onset type 1 diabetes (T1D), the insulin-dose adjusted Hemoglobin A1c (IDAA1c) of ≤9, is superior to a new tool, total daily dose of insulin (TDD) of

METHODS: A retrospective analysis of 204 subjects of ages 2-14 years, mean age 7.9±3.2 years, (male 7.8±3.4 years, [n=98]; female 7.9±3.0 years, [n=106], p=0.816) with new-onset T1D. Anthropometric and biochemical data were collected for the first 36 months of disease. PCR was defined by both IDAA1c≤9 and TDD

RESULTS: There were 86 (42.2%) (age 9.1±3.0 years; …

A Predictive Model For Lack Of Partial Clinical Remission In New-Onset Pediatric Type 1 Diabetes, Katherine R. Marino, Rachel L. Lundberg, Aastha Jasrotia, Louise Maranda, Michael J. Thompson, Bruce A. Barton, Laura C. Alonso, Benjamin U. Nwosu

Benjamin U. Nwosu

IMPORTANCE: >50% of patients with new-onset type 1 diabetes (T1D) do not enter partial clinical remission (PCR); early identification of these patients may improve initial glycemic control and reduce long-term complications. AIM: To determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D. SUBJECTS AND METHODS: Data on remission were collected for the first 36 months of disease in 204 subjects of ages 2-14 years with new-onset type 1 diabetes. There were 86 remitters (age 9.1±3.0y; male 57%), and 118 non-remitters (age 7.0±3.1y; male 40.7%). PCR was defined as insulin-dose adjusted hemoglobin A1c of ≤9. …

Vitamin D Status In Pediatric Irritable Bowel Syndrome, Benjamin U. Nwosu, Louise Maranda, Ninfa Candela

Benjamin U. Nwosu

IMPORTANCE: Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear. AIM: To characterize the vitamin D status of pediatric patients with IBS using a case-control study design. HYPOTHESIS: Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls. SUBJECTS AND METHODS: A retrospective …

Adiposity Is Associated With Early Reduction In Bone Mass In Pediatric Inflammatory Bowel Disease, Nithya Setty-Shah, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear.

Aims: To determine the role of adiposity on bone mass in the first 3 years of diagnosis of IBD.

Hypothesis: Increased adiposity will be associated with increased bone mass in both the controls and IBD subjects.

Setting: University tertiary institution.

Methods: Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70y, diagnosed with IBD for < 4 years were compared to 24 controls, age 13.65 ± 2.60y. Overweight was defined as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^thpercentile. Severity of IBD was determined by the Pediatric …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Adjunctive Metformin Therapy In Overweight/Obese Youth With Type 1 Diabetes, Benjamin U. Nwosu, Louise Maranda, Karen Cullen, Lisa Greenman, Jody Fleshman, Nancy Mcshea, Bruce A. Barton, Mary M. Lee

Benjamin U. Nwosu

CONTEXT: Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.

OBJECTIVE: To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.

HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.

DESIGN, SETTING, AND PARTICIPANTS: A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of …

Increased Risk For Vitamin D Deficiency In Obese Children With Both Celiac Disease And Type 1 Diabetes, Nithya Setty-Shah, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background. It is unknown whether the coexistence of type 1 diabetes (T1D) and celiac disease (CD) increases the risk for vitamin D deficiency.

Aims. To determine the vitamin D status and the risk for vitamin D deficiency in prepubertal children with both T1D and CD compared to controls, TID, and CD.

Subjects and Methods. Characteristics of 62 prepubertal children of age 2–13 y with either CD + T1D (� = 22, 9.9 ± 3.1 y), CD only (� = 18, 8.9 ± 3.3 y), or T1D only (� = 22, 10.1 ± 2.8 y) were compared to 49 controls of …

The Vitamin D Status In Inflammatory Bowel Disease, Lauren Veit, Louise Maranda, Jay G. Fong, Benjamin U. Nwosu

Benjamin U. Nwosu

CONTEXT: There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

AIM: To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

HYPOTHESIS: Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

SUBJECTS AND METHODS: A case-controlled retrospective study of subjects with IBD (n = 58) of 2-20 years (male n = 31, age 16.38±2.21 years; female n = 27, age16.56±2.08 years) and healthy controls (n = 116; male n = 49, age 13.90±4.59 years; female n …

The Effects Of Vitamin D Supplementation On Hepatic Dysfunction, Vitamin D Status, And Glycemic Control In Children And Adolescents With Vitamin D Deficiency And Either Type 1 Or Type 2 Diabetes Mellitus, Benjamin U. Nwosu, Louise Maranda

Benjamin U. Nwosu

BACKGROUND: The effects of vitamin D supplementation on mild hepatic dysfunction and glycemic control are unclear in children and adolescents with either type 1 (T1D) or type 2 diabetes (T2D).

HYPOTHESIS: Vitamin D supplementation will improve hepatic dysfunction and glycemic control.

AIM: To determine the effect of vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c), and serum 25-hydroxyvitamin D [25(OH)D] concentration.

SUBJECTS AND METHODS: A retrospective study of 131 subjects with either T1D (n = 88∶46 females, 42 males), or T2D (n = 43∶26 females, 17 males) of ages 3-18 years between 2007-2013. All subjects had (1) a …

The Relationship Between Subnormal Peak-Stimulated Growth Hormone Levels And Auxological Characteristics In Obese Children, Jefferson Barrett, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology.

Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST).

Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) < 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers.

Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion …

The Relationship Between Subnormal Peak-Stimulated Growth Hormone Levels And Auxological Characteristics In Obese Children, Jefferson Barrett, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology. Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST). Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) < 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers. Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion criteria: GHST using arginine and clonidine. Exclusion criteria: hypopituitarism, abnormal pituitary magnetic resonance imaging scan, syndromic obesity, or syndromic short stature. Data were expressed as mean ± SD. Results: The over-weight/obese children with peak GH of <10 μg/L had significantly lower value for natural log (ln) peak GH (1.45 ± 0.09 vs. 1.83 ± 0.35, p = 0.022), but similar values for GV SDS, insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone age, BA − CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight peers with GHD. After adjusting for covariates, the over-weight/obese children (BMI ≥ 85th percentile) were >7 times more likely than normal-weight subjects (BMI < 85th percentile) to have a peak GH of <10 μg/L, and 23 times more likely to have a peak GH of <7 μg/L (OR = 23.3, p = 0.021). There was a significant inverse …

The Vitamin D Status Of Prison Inmates, Benjamin U. Nwosu, Louise Maranda, Rosalie Berry, Barbara Colocino, Carlos D. Flores, Kerry Folkman, Thomas Groblewski, Patricia Ruze

Benjamin U. Nwosu

INTRODUCTION: There is no comprehensive, systematic analysis of the vitamin D status of prisoners in the scientific literature.

OBJECTIVE: To investigate the vitamin D status and its determinants in US prison inmates.

HYPOTHESIS: Given the uniformity of dietary intake amongst inmates, vitamin D status will be determined by non-dietary factors such as skin pigmentation, security level-, and the duration of incarceration.

SUBJECTS AND METHODS: A retrospective study of 526 inmates (males, n = 502, age 48.6±12.5 years; females, n = 24, age 44.1±12.2) in Massachusetts prisons. Vitamin D sufficiency, insufficiency, and deficiency were respectively defined as a 25(OH)D concentration 75 …

Lactose Intolerance: Lack Of Evidence For Short Stature Or Vitamin D Deficiency In Prepubertal Children, Nithya Setty-Shah, Louise S. Maranda, Ninfa Candela, Jay G. Fong, Idris Dahod, Alan D. Rogol, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: The health consequences of lactose intolerance (LI) are unclear. Aims: To investigate the effects of LI on stature and vitamin D status. Hypotheses: LI subjects will have similar heights and vitamin D status as controls. Subjects and Methods: Prepubertal children of ages 3-12 years with LI (n=38, age 8.61 ± 3.08y, male/female 19/19) were compared to healthy, age- and gender-matched controls (n=49, age 7.95±2.64, male/female 28/21). Inclusion criteria: prepubertal status (boys: testicular volume Results: There was no significant difference in 25(OH)D between the LI and non-LI subjects (60.1±21.1, vs. 65.4 ± 26.1 nmol/L, p = 0.29). Upon stratification into …

Vitamin D Status Is Associated With Early Markers Of Cardiovascular Disease In Prepubertal Children, Benjamin U. Nwosu, Louise Maranda, Karen Cullen, Carol A. Ciccarelli, Mary M. Lee

Benjamin U. Nwosu

Background: The associations of 25-hydroxyvitamin D [25(OH)D], non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL), and related markers of early cardiovascular disease (CVD) are unclear in prepubertal children.

Objective: To investigate the association of 25(OH)D with markers of CVD. The hypothesis was that 25(OH)D would vary inversely with non-HDL-C.

Subjects and methods: A prospective cross-sectional study of children (n=45; 26 males, 19 females) of mean age 8.3 ± 2.5 years to investigate the relationships between 25(OH)D and glucose, insulin, high-sensitivity C-reactive protein, and lipids. Vitamin D deficiency was defined as 25(OH)D/mL; overweight as body mass index (BMI) ≥ 85 th but …

The Relationship Between Adiposity And Stature In Prepubertal Children With Celiac Disease, Benjamin U. Nwosu, Rachel I. Snook, Louise S. Maranda

Benjamin U. Nwosu

Background and Aim: The pathogenesis of short stature in celiac disease (CD) is unknown. Obese children are generally taller than their non-obese peers; however, the role of adiposity on stature in CD is unclear. Our aim was to determine the association between adiposity and stature in CD.

Subjects and methods: We compared the anthropometric characteristics of prepubertal children of ages 3-12 years, with biopsy-proven CD (n=40) and who were not on gluten-free diet, to same aged, prepubertal non-CD children (n=50). Body mass index (BMI) was calculated using the formula weight/height2. Sex-adjusted midparental target height (MPTH) standard deviation score (SDS) was …

Double Diabetes: The Search For A Treatment Paradigm In Children And Adolescents, Benjamin U. Nwosu

Benjamin U. Nwosu

Discusses double diabetes -- the coexistence of features of both type 1 and type 2 diabetes in the same individual -- with a comprehensive discussion of the various aspects of this disorder and a focus on the search for a treatment paradigm in children and adolescents.

Double Diabetes: The Evolving Treatment Paradigm In Children And Adolescents, Benjamin U. Nwosu

Benjamin U. Nwosu

The global pandemic of obesity in children and adolescents has resulted in a new expression of diabetes mellitus designated as double diabetes. The entity encompasses the autoimmune load of Type 1 Diabetes and the metabolic load of Type 2 Diabetes. There is no consensus on the best therapeutic modality for this new expression of diabetes mellitus. Optimal therapeutic options must address the coexistence of both metabolic and autoimmune components of diabetes mellitus in the patient. There have also been calls to revise the current classification of diabetes mellitus to take into account the surging prevalence of double diabetes in children …

Serum 25-Hydroxyvitamin D Levels Do Not Correlate With Asthma Severity In A Case-Controlled Study Of Children And Adolescents, Jennifer Menon, Louise Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: There is no consensus on the association between vitamin D and asthma.

Objective: To determine the relationship between 25-hydroxyvitamin D [25(OH)D] levels and asthma symptom severity in children and adolescents.

Methods: A retrospective, case-control study of 263 subjects of ages 2–19 years with asthma who were compared to 284 non-asthmatic controls of similar ages. Subjects were excluded if they had diseases of calcium or vitamin D metabolism or were receiving calcium or vitamin D supplementation. Serum 25(OH)D was measured in all subjects. Asthma symptom severity, usually stratified into 6 steps, was stratified into five steps [1–5] based on the …

Is Vitamin D Deficiency A Feature Of Pediatric Celiac Disease?, Jeffrey Villanueva, Louise Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: Celiac disease (CD) is an autoimmune enteropathy characterized by villus atrophy and malabsorption of essential nutrients. Vitamin D deficiency has been described in autoimmune diseases, but its status in prepubertal children with CD has not been adequately studied.

Objective: To determine the vitamin D status of prepubertal children with CD.

Study design: A retrospective study of prepubertal children aged 3–12 years with CD (n=24) who were compared to prepubertal, non-CD children of the same age (n=50). Children were included in the study if they had a diagnosis of CD by intestinal biopsy, and were not on a gluten-free diet …

Does Hepatic Dysfunction Worsen Glucose Homeostasis By Impairing Vitamin D Metabolism?, Benjamin U. Nwosu

Benjamin U. Nwosu

The Management of diabetes mellitus (DM) remains an enigma even though the symptoms of the disease had been described more than 3000 years ago. This is because the central therapeutic goal of DM therapy, euglycemia, is influenced by complex physiologic and pathologic processes, some of which are clearly understood, while others are less clear. Suboptimal glycemic control is a recognized risk factor for acute and chronic complications of diabetes including microvascular and macrovascular diseases. The central question for this editorial is whether mild hepatic dysfunction could impair vitamin D metabolism and secondarily lead to sub-optimal glycemic control.

A Potential Role For Adjunctive Vitamin D Therapy In The Management Of Weight Gain And Metabolic Side Effects Of Second-Generation Antipsychotics, Benjamin U. Nwosu, Bruce Meltzer, Louise Maranda, Carol A. Ciccarelli, Daniel Reynolds, Laura A. Curtis, Jean A. King, Jean A. Frazier, Mary M. Lee

Benjamin U. Nwosu

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best …

Pseudohypoparathyroidism In Children, Benjamin U. Nwosu

Benjamin U. Nwosu

Summary: Albright hereditary osteodystrophy (AHO) is a genetic syndrome characterized by a distinctive set of developmental and skeletal defects that may easily be misdiagnosed as exogenous obesity in children. There are very few publications detailing the comprehensive management of children and adolescents with this disorder. This chapter provides a comprehensive discussion of the various aspects of this disorder. At the end, the reader should be able to: (1) List the clinical features of Albright hereditary osteodystrophy, (2) Identify the genetic and molecular abnormalities of AHO, (3) List the clinical features of pseudohypoparathyroidism type 1a (PHP 1a), (4) Describe the management …

A Novel Activating Mutation In Transmembrane Helix 6 Of The Thyrotropin Receptor As Cause Of Hereditary Nonautoimmune Hyperthyroidism, Benjamin U. Nwosu, Loukas Gourgiotis, Marvin C. Gershengorn, Susanne Neumann

Benjamin U. Nwosu

Constitutively-activating germline mutations of the thyrotropin receptor (TSHR) gene are very rare and are considered the cause of hereditary nonautoimmune hyperthyroidism. We describe four affected individuals from a Caucasian family: a mother and her three children, and an unaffected father. The mother and her first two children presented in a similar manner: lifelong histories of heat intolerance, hyperactivity, fast heart rate, reduced energy, increased appetite, and scrawny build. They all developed goiter in childhood and showed a suppressed TSH and elevated thyroxine (T(4)). The last child, a 12-year-old female, presented with no clinical symptoms or palpable neck mass, but with …