Type 2 diabetes in youth: are there racial differences in β‐cell responsiveness relative to insulin sensitivity?

Bacha F, Gungor N, Lee S, Arslanian SA. Type 2 diabetes in youth: are there racial differences in β‐cell responsiveness relative to insulin sensitivity? Objective: Non‐diabetic African American (AA) youth have an upregulated insulin secretion relative to insulin sensitivity (IS) compared with their American White (AW) peers. We investigated if similar racial differences exist in youth with T2DM. Research Design and Methods: Fourteen AAs and 14 AWs T2DM adolescents underwent evaluation of IS and clearance (hyperinsulinemic–euglycemic clamp), first‐ and second‐phase insulin and C‐peptide secretion (hyperglycemic clamp); body composition (DEXA); and abdominal adiposity (CT). Results: AA and AW T2DM had similar HbA1c, diabetes duration, BMI, and % body fat, with lower visceral fat in AAs (p = 0.013). While insulin‐stimulated glucose disposal was similar in AA and AW (7.5 ± 1.0 vs. 7.3 ± 0.9 mg/kg FFM/min), IS tended to be lower (2.5 ± 0.4 vs. 3.8 ± 0.6 mg/kg FFM/min per µU/mL, p = 0.081). First‐phase insulin (175.7 ± 52.9 vs. 66.6 ± 10.8 µU/mL, p = 0.01) and second‐phase insulin (236.2 ± 40.7 vs. 105.1 ± 17.9 µU/mL, p = 0.008), and first‐phase C‐peptide (8.2 ± 1.2 vs. 5.0 ± 0.3 ng/mL, p = 0.02) and second‐phase C‐peptide (10.8 ± 0.9 vs. 7.6 ± 0.6 ng/mL, p = 0.012) were higher in AA. β‐Cell function relative to IS was higher in AA vs. AW (259.5 ± 35.3 vs. 168.8 ± 25.1 mg/kg FFM/min, p = 0.043). Conclusions: Racial differences in insulin secretion can be demonstrated with the clamp technique in obese adolescents with T2DM. Similar to non‐diabetic youth, AA adolescents with T2DM compared with their AW counterparts have an upregulated β‐cell function relative to IS, the reasons for which remain to be investigated.     

Is phototherapy exposure associated with better or worse outcomes in 501‐ to 1000‐g‐birth‐weight infants?

Aim: To compare risk‐adjusted outcomes at 18‐ to 22‐month‐corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy. Methods: Outcomes at 18 to 22‐month‐corrected age included death, neurodevelopmental impairment (NDI) and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for centre and other potentially confounding variables. Results: Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501‐ to 1000‐g‐BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI: 0.60–1.20), death or adverse neurodevelopmental endpoints. However, among infants 501–750 g BW, the rate of significant developmental impairment with MDI < 50 was significantly higher for NoPTx (29%) than PTx (12%) (p = 0.004). Conclusions: Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded because of bias from deaths before reaching conservative treatment threshold. The higher rate of MDI < 50 in the 501‐ to 750‐g‐BW NoPTx group is concerning and consistent with NRN Trial results.     

Asthma symptoms in early childhood – what happens then?

Aim: To study the outcome in early adulthood for children with early asthma symptoms and to analyse the factors associated with current asthma. Methods: In a prospective study, we have re-investigated 89/101 children who were hospitalized before the age of two years due to wheezing. The children were investigated using a questionnaire and allergy and bronchial hyper-responsiveness tests at the age of 17-20 years and compared with age-matched controls. Results: In the cohort, 43% had had asthma symptoms in the preceding 12 months compared with 15% in the control group. The strongest risk factors for asthma were current allergy, bronchial hyper-responsiveness and female gender. Female gender and passive smoking in infancy were independent infantile risk factors. In addition to female gender, two pathways led to current asthma: an allergic pathway from family atopy via the development of allergy and another pathway from early passive smoking via hyper-responsiveness and active smoking.

Conclusion: In children with early wheezing disorder, current allergy, bronchial hyper-responsiveness and female gender were the strongest risk factors for asthma in early adulthood, while female gender and passive smoking in infancy were independent infantile risk factors. The effects of early passive smoking persist longer than previously reported.     

Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight ≤1250 g?

AIM: To compare the long-term growth and neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birthweight (BW) < or = 1250 g) with necrotising enterocolitis (NEC) with BW-matched controls. METHODS: This is a case control study performed at a regional tertiary care neonatal intensive care unit. Infants with stage II or III NEC admitted to a regional tertiary care neonatal unit between 1995 and 2000 were identified. Each infant with NEC was matched by BW (+/-100 g) to next two infants admitted in the unit without NEC. Growth and neurodevelopmental outcomes at 36 months are compared. RESULTS: In total, 51 infants with NEC and 102 controls met study eligibility criteria and 146/153 (94.3%) were prospectively followed for 36 months. Infants with NEC had more culture-proven sepsis (35.3% vs. 10.8%, P < 0.001); patent ductus arteriosus requiring therapy (64.7% vs. 45%, P = 0.02), chronic lung disease (60.7% vs. 45%, P = 0.04) and longer hospital stay (84 days vs. 71 days, P < 0.0001). There were no significant differences in growth outcomes between the two groups at 36 months. Overall 24% of infants with NEC had one major neurodevelopmental disability compared with 10% among control infants. Infants who developed NEC had significantly higher cognitive delay (i.e. cognitive index <70) and visual impairment. A logistic regression model identified NEC as a predictor of cognitive delay. CONCLUSION: Preterm infants who develop NEC are at a significantly higher risk for developing neurodevelopmental disability. We recommend close neurodevelopmental follow up for all < or =1250 g infants who develop stage II or III NEC.     

A future for neonatal α1‐antitrypsin screening?

A WHO expert group recommends neonatal screening for alpha1-antitrypsin deficiency (alpha1ATD). Homozygous alpha1ATD PiZZ occurs in 1 in 5000 of the U.S. Caucasian population and up to 1 in 500 individuals of the European population, with a large regional variation. It is a risk factor that predisposes mainly to liver disease in early infancy and emphysema in early adulthood. Most importantly, smoking decreases the duration of the asymptomatic phase and life expectancy by 10-20 y. The Swedish alpha1AT screening programme and subsequent information and advice prevented the majority of adolescents from starting to smoke. The involved parents and alpha1ATD adolescents retrospectively recommended neonatal screening. Potential advantages of neonatal alpha1AT screening are: early diagnosis and treatment of neonatal liver disease, optimal treatment of fever and bacterial infections theoretically preventing liver cell damage, genetic advice and information about the consequences of passive and active smoking. Potential advantages of postponing screening until age 11-12y are: identification of alpha1ATD close to the age when smoking may start, and possibility for the child to take part in the screening decision. Disadvantages of alpha1AT screening are: psychosocial reactions--the mother probably being most vulnerable in the neonatal period--and discrimination by insurance companies and employers. Important uncertainties are: lack of knowledge concerning participation in a voluntary alpha1AT screening, psychosocial reactions and the efficacy of anti-smoking advice if the information is given to school-age children and families. Thus the question whether and when to screen for alpha1ATD is still the topic of lively debate.     

A future for neonatal α1‐antitrypsin screening?*

A WHO expert group recommends neonatal screening for alpha1-antitrypsin deficiency (alpha1ATD). Homozygous alpha1ATD PiZZ occurs in 1 in 5,000 of the U.S. Caucasian population and up to 1 in 500 individuals of the European population, with a large regional variation. It is a risk factor that predisposes mainly to liver disease in early infancy and emphysema in early adulthood. Most importantly, smoking decreases the duration of the asymptomatic phase and life expectancy by 10-20 y. The Swedish alpha1AT screening programme and subsequent information and advice prevented the majority of adolescents from starting to smoke. The involved parents and alpha1ATD adolescents retrospectively recommended neonatal screening. Potential advantages of neonatal alpha1AT screening are: early diagnosis and treatment of neonatal liver disease, optimal treatment of fever and bacterial infections theoretically preventing liver cell damage, genetic advice and information about the consequences of passive and active smoking. Potential advantages of postponing screening until age 11-12 y are: identification of alpha1ATD close to the age when smoking may start, and possibility for the child to take part in the screening decision. Disadvantages of alpha1AT screening are: psychosocial reactions-the mother probably being most vulnerable in the neonatal period-and discrimination by insurance companies and employers. Important uncertainties are: lack of knowledge concerning participation in a voluntary alpha1AT screening, psychosocial reactions and the efficacy of anti-smoking advice if the information is given to school-age children and families. Thus the question whether and when to screen for alpha1ATD is still the topic of lively debate.     

“What if?”: Addressing uncertainty with families

Children with cancer and their families deal with uncertainty throughout their treatment course. Clinicians must help patients and families manage uncertainty by engaging them in discussions about their worries and fears. Too often, clinicians avoid or defer discussions about anticipated or worried‐about future events—the “what ifs.” Failing to engage in these conversations may lead to increased distress. We have developed a framework for having “what if” conversations with patients and families that enables providers to explore families’ informational and emotional needs. This framework may enable providers to improve families’ prognostic understanding, explore concerns, and examine preferences and goals of care.     

Differences in β‐cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role?

Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated β‐cell function and insulin hypersecretion, in response to intravenous (iv) glucose, compared with Whites. To investigate if the same holds true during an oral glucose challenge and because of the important role of glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) in augmenting insulin secretion, we examined β‐cell function and incretin hormones in 85 Black and 78 White obese adolescents, with normal glucose tolerance (NGT), during a 2‐h oral glucose tolerance test (OGTT) with mathematical modeling of plasma glucose and C‐peptide concentrations to assess β‐cell glucose sensitivity (βCGS), rate sensitivity, potentiation factor, and insulin sensitivity. Incretin, pancreatic polypeptide, and glucagon concentrations were measured during the OGTT. Black obese youth had a heightened early insulin secretion together with significantly greater βCGS, rate sensitivity, and potentiation factor compared with Whites, with no differences in incretin and glucagon concentrations. Basal and stimulated insulin clearance was lower (p = 0.001) in Black vs. White youth. In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened β‐cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in β‐cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth.     

Meningococcal pericarditis in a 2‐year‐old child: Reactive or infectious?

Pericarditis is an uncommon manifestation of infection of Neisseria meningitidis. Pericarditis may be caused by direct invasion or immune-complex-mediated (reactive) inflammation. We outline the case of a two-year-old girl with probable reactive pericarditis, review the cases reported in the English literature since 1966 and discuss the pathogenesis of meningococcal pericarditis.     

Non‐tuberculous mycobacterial lymphadenitis in healthy children: another “lifestyle disease”?

An increasing incidence of non-tuberculous mycobacterial (NTM) lymphadenitis has been reported in previously healthy children in the western world since about 1985. In this study we investigated the sociodemographic and individual characteristics of these patients. Information about patients was collected prospectively from 1977 to 1996. For comparison, an ad hoc group of hospitalized children with bacterial cervical lymphadenitis was chosen. In addition to individual characteristics, information was collected on the country of birth of the patients and their parents, and the socioeconomic characteristics of the domicile area. We identified 81 children with NTM, 14 with tuberculous and 192 with septic lymphadenitis. Significantly more parents of children with NTM than in either of the other two groups were Swedish-born and lived in privileged socioeconomic areas. CONCLUSION: The increase in NTM lymphadenitis in healthy children has taken place at the same time as the reported increase in atopic disease and asthma in childhood. Both groups of patients seem to come from favourable living conditions. It is speculated that NTM lymphadenitis, like asthma and certain other diseases triggered by the immune system, might be a "lifestyle disease".