Ricardo Gomez

Predictors of glycemic control in children with Type 1 diabetes : the importance of race

Diabetes is a common cause of kidney failure and blindness among young adults, particularly of African-American descent. Since glycemic control is a predictor of diabetes complications, we evaluated the impact of multiple factors including a special multidisciplinary management program on glycosylated hemoglobin in children with Type 1 diabetes. Data was collected from pediatric diabetes clinics in New Orleans, LA and Baltimore, MD. In New Orleans, hemoglobin A(1c) was higher in African-American patients 12. 5+/-3.3% (n=71) vs. 10.7+/-2.1% (n=80) in Caucasian children, p<0. 0001. Longer duration of diabetes was also associated with higher hemoglobin A(1c) in both races. The effect of race on hemoglobin A(1c) was independent of the influence of sex, insurance status, body mass index (BMI) z-score, and number of clinic visits. Covariate analysis with mean blood glucose levels indicated that higher hemoglobin A(1c) was attributable to higher mean blood glucose levels in African-American children. From the Baltimore data, a multidisciplinary intervention program led to improved total glycosylated hemoglobin for Caucasian patients but not for African-American children. Poorer glycemic control of African-American children is likely to predispose them to a higher likelihood of developing microvascular complications as they mature. Standard hospital-based multidisciplinary programming for diabetes management may have limited effectiveness in improving glycemic control of African-American children with diabetes. Innovative intervention programs are needed for these high-risk patients.

Helicobacter pylori infection and insulin requirement among children with type 1 diabetes mellitus.

Objective. Helicobacter pylori induces gastric inflammation and the production of cytokines in infected individuals. Theoretically, this increased production of cytokines could be deleterious for the control of the glycemia of patients with diabetes. This study aimed to describe the insulin requirement among patients with type 1 diabetes and H pylori infection compared with uninfected counterparts. Methods. Cross-sectional design. Demographic information (age, gender, race, annual family income, and number of individuals per room in the household) and clinical information (age at diagnosis of diabetes, duration of illness, weight, height, compliance with clinical appointments, daily insulin units per kilogram of body weight [IU/kg/d], and glycosylated hemoglobin A level) was obtained from children and adolescents with diagnosis of type 1 diabetes mellitus who were seen at Childrens Hospital in New Orleans. A total of 2 mL of blood was also collected and sera were tested forH pylori-specific immunoglobulin G antibodies using an enzyme immunoassay. The daily insulin requirement among infected and uninfected children was compared, and the effect of other variables was evaluated with multiple linear regression. Results. Of the 71 subjects who were evaluated (median age: 11 years), 11 (15.5%) were found to be infected. H pylori infection was more frequent among subjects who were older, who had a lower family income, and who were black. Infected children were found to require more insulin (1.2 vs 0.9 IU/Kg/d) and their glycosylated hemoglobin A level was higher (14.9 vs 11.8) than the level found in uninfected subjects. Multiple linear regression analysis identified H pylori infection duration of illness, race (black), body mass index, and gender (female), to be associated independently with increased daily insulin requirement (IU/kg/d). Conclusion. In our study population, children with type 1 diabetes and H pylori infection had an increased daily insulin requirement compared with the requirement of their uninfected peers. The reason for this association requires additional investigation.

HERV-K10s and Immune-Mediated (Type 1) Diabetes

(A) HTDV/HERV-K particles expressed in human teratocarcinoma cells. Ultrathin section, (B) immunolabeling with goat anti HERV-K Gag antibody in ultrathin frozen section (right). Bar represents 250 nm

Poor glycemic control is associated with increased diastolic blood pressure and heart rate in children with Type 1 diabetes

Although higher levels of hemoglobin A1c (HbA1c) and blood pressure precede the development of nephropathy in Type 1 diabetes (T1DM), the relationship between glycemic control and cardiovascular factors early in the course of diabetes is not clear. We conducted a retrospective study from clinic data for a 1-year period in 148 children with T1DM aged 12.5+/-4.4 years who had average diabetes duration of 4.5+/-3.3 years. The influence of HbA1c and reported insulin dose on blood pressure and heart rate were analyzed in multivariate linear regression models, statistically adjusted for the effect of race, sex, age, body mass index, and duration of diabetes. There was a significant positive correlation of mean HbA1c with mean diastolic blood pressure (P<.025) and mean heart rate (P<.0004). Higher diastolic blood pressure and heart rate were associated with higher HbA1c. Increased insulin doses were also associated with increased diastolic blood pressure (P<.009) and heart rate (P<.013). Insulin dose and HbA1c were also significantly correlated (P<.001). There was no correlation between mean HbA1c and mean systolic blood pressure. Increased levels of HbA1c and insulin dose are associated with increased diastolic blood pressure and heart rate. Although within the normal range, early increases of diastolic blood pressure and heart may indicate early cardiovascular changes in response to diabetes and potentially contribute to a greater proclivity for later development of nephropathy.

Racial differences in neighborhood disadvantage, inflammation and metabolic control in black and white pediatric type 1 diabetes patients

Racial variation in the relationship between blood glucose and hemoglobin A1c (HbA1c) complicates diabetes diagnosis and management in racially mixed populations. Understanding why HbA1c is persistently higher in blacks than whites could help reduce racial disparity in diabetes outcomes.

Association between Helicobacter felis—Induced Gastritis and Elevated Glycated Hemoglobin Levels in a Mouse Model of Type 1 Diabetes

Helicobacter pylori infection has been described in association with increases in glycated hemoglobin (HbA(1c)) levels in patients with type 1 diabetes. The purpose of the present study was to use an animal model of Helicobacter infection to test, under controlled conditions, the hypothesis that infection is associated with high HbA(1c) levels. Diabetes was induced in C57BL/6 mice by administration of streptozotocin, and the mice were orally inoculated with H. felis. Six weeks after inoculation, infected mice (n=10) showed gastritis scores significantly greater (P=.01) than those of uninfected mice (n=10). HbA(1c) levels were significantly higher in infected mice with gastritis (11.6%; n=6) than in infected mice without gastritis (8.4%; n=4) or uninfected mice (7.6%; n=10). It was concluded that gastritis induced by H. felis is associated with increased HbA(1c) levels in the mouse model of streptozotocin-induced diabetes.

Differences in Red Blood Cell Indices Do Not Explain Racial Disparity in Hemoglobin A1c in Children with Type 1 Diabetes

We assessed the association of erythrocyte indices on mean blood glucose-independent racial disparity in hemoglobin A1c (HbA1c) in youth with type 1 diabetes. Blacks still had higher HbA1c after adjustment for mean blood glucose, red blood cell indices, age, and sex. Such differences need to be taken into account when interpreting HbA1c in Black patients.

Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia.

Neonatal severe hyperparathyroidism (NSHPT) is a rare, life-threatening condition that presents with severe hypercalcemia, hyperparathyroidism, and osteopenia in the newborn period. Treatment of NSHPT traditionally includes hydration and bisphosphonates; however newer calcimimetic agents, such as cinacalcet, are now being utilized to prevent or delay parathyroidectomy which is technically difficult in the newborn. Medical treatment success is related to calcium sensing receptor (CaSR) genotype. We report a 4-day-old infant who presented with hyperbilirubinemia, poor feeding, weight loss, severe hypotonia and was ultimately diagnosed with NSHPT. The patients total serum calcium level of 36.8 mg/dL (reference range: 8.5-10.4 mg/dL) is, to our knowledge, the highest ever documented in this setting. Exome data previously obtained on the infants parents was re-analyzed demonstrating bi-parental heterozygosity for a mutation of the CASR gene: c.206G > A, and Sanger sequencing data confirmed the patient was a homozygote for the same mutation. Though a patient with the same CaSR gene mutation described here has responded to cinacalcet, our patient did not respond and required parathyroidectomy. Though this case has previously been published as a surgical case report, a full report of the medical management and underlying genetic etiology is warranted; this case underscores the importance of disclosing bi-parental heterozygosity for a gene causing severe neonatal disease particularly when treatment is available and illustrates the need for further in vitro studies of this CaSR mutation.

Intima-media thickness at different arterial segments in pediatric type 1 diabetes patients and its relationship with advanced glycation end products

Patients with type 1 diabetes mellitus (T1DM) are at risk for premature atherosclerosis (AS), which has its origin in childhood. Carotid intima‐media thickness (IMT) is an established surrogate marker for subclinical AS in adults. The first macroscopically detectable AS changes, however, begin in the abdominal aorta. Advanced glycation end products (AGE) predict microvascular complications in diabetes.

Hemoglobin A1c, frequency of glucose testing and social disadvantage: Metrics of racial health disparity in youth with type 1 diabetes

INTRODUCTION Black youth with type 1 diabetes (T1D) have higher HbA1c than whites. To understand HbA1c differences, we examined the relationship of psycho-social factors and glucose testing with HbA1c. METHODS Glucose tests per day (BGs/d) and mean blood glucose (MBG) were calculated from meter data of youth self-identified as black (n = 33) or white (n = 53) with T1D. HbA1c, family income, insurance status, concentrated disadvantage (CDI), psychological depression (DSC), mother educational attainment (MEA), and insulin delivery method (IDM) data was were analyzed. RESULTS Black patients had significantly higher HbA1c, MBG and disadvantage measures compared to whites. BGs/d correlated with HbA1c, MBG, age and CDI. Race (p < 0.0158), age (p < 0.0001) and IDM (p < 0.0036) accounted for 50% of the variability (R2 = 0.5, p < 0.0001) in BGs/d. Regardless of age, black patients had lower BGs/d than whites. MBG (p < 0.0001) and BGs/d (p < 0.0001) accounted for 61% of the variance in HbA1c (p < 0.0001). CONCLUSIONS BGs/d is easily assessed and closely associated with HbA1c racial disparity. BGs/d is intricately linked with greater social disadvantage. Innovative management approaches are needed to overcome obstacles to optimal outcomes.