To determine the course of glycemic decline in a pediatric cohort with type 2 diabetes mellitus (T2DM) by defining longitudinal changes in hemoglobin A1c (HbA1c) and insulin requirement. We also followed markers of insulin reserve (fasting C-peptide and IGFBP-1) over time.
Participants included two groups: (1) T2DM Nonacidotic (NA) (n = 46); and (2) T2DM diabetic ketoacidosis (n = 13). HbA1c, insulin dose, and fasting C-peptide and IGFBP-1 were obtained at baseline and every 6 months for 4 years.
At baseline, Mann Whitney tests demonstrated that the diabetic ketoacidosis group had higher HbA1c (P = .002), required more insulin (P = .036), and had lower C-peptide (P = .003) than the NA group. Baseline insulin dose (Spearman r = -0.424, P = .009) and baseline IGFBP-1 (Spearman r = -0.349, P = .046) correlated negatively with C-peptide. Over time, HbA1c, insulin dose, and C-peptide changed significantly in a complex manner, with group differences. HbA1c reached a nadir at 6 to 12 months and began to rise after 1.5 years. Insulin requirements reached a nadir at 1 year and began to rise after 2 years.
Unlike adults, children with T2DM require increasing insulin doses over a 4-year period, and diabetic ketoacidosis at diagnosis predicts greater β-cell decline over time.
[Show abstract][Hide abstract] ABSTRACT: Isolated congenital asplenia (ICA) is a rare condition at risk for overwhelming infection. When complicated by invasive infection, the mortality remains high, at greater than 60%. We describe a girl with ICA who developed recurrent meningitis by three different pathogens. The first, meningitis by Escherichia coli, occurred 4 days after premature birth. The other two pathogens were serotype 6B Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), at 18 and 25 months of age, respectively. The patient was successfully treated with prompt antimicrobial therapy in all episodes. Serum anti-polyribosylribitol phosphate (PRP) and anti-6B-type pneumococcal antibodies were below the levels for protective activity after natural infections. Although anti-PRP antibody was significantly increased after Hib vaccination, two (6B and 19F) of seven serotype-specific pneumococcal antibodies were not elevated to protective levels after the second 7-valent pneumococcal conjugate vaccine (PCV7). We, therefore, added a third PCV7. To our knowledge, this is the first neonatal ICA patient with invasive infection and the first case of bacterial meningitis occurring three times. Our findings indicate that monitoring of immune responses after natural infections and vaccinations, and reevaluations of vaccine schedule, are important for ICA patients to prevent subsequent invasive infections.
Journal of Infection and Chemotherapy 11/2011; 18(4):576-80. DOI:10.1007/s10156-011-0341-z · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate remaining life expectancy (RLE), quality-adjusted life expectancy (QALE), causes of death and lifetime cumulative incidence of microvascular/macrovascular complications of diabetes for youths diagnosed with Type 2 diabetes.
A Markov-like computer model simulated the life course for a hypothetical cohort of adolescents/young adults in the USA, aged 15-24 years, newly diagnosed with Type 2 diabetes following either conventional or intensive treatment based on the UK Prospective Diabetes Study. Outcomes included RLE, discounted QALE in quality-adjusted life years (QALYs), cumulative incidence of microvascular/macrovascular complications and causes of death.
Compared with a mean RLE of 58.6 years for a 20-year-old in the USA without diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44 discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44 discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence of all microvascular complications and lower mortality from microvascular complications (e.g. end-stage renal disease (ESRD) death 19.4% vs. 25.2%). Approximately 5% with both treatments had ESRD within 25 years. Lifetime cumulative incidence of coronary heart disease (CHD) increased with longer RLE and greater severity of CHD risk factors. Incorporating disutility (loss in health-related quality of life) of intensive treatment resulted in net loss of QALYs.
Adolescents/young adults with Type 2 diabetes lose approximately 15 years from average RLE and may experience severe, chronic complications of Type 2 diabetes by their 40s. The net clinical benefit of intensive treatment may be sensitive to preferences for treatment. A comprehensive management plan that includes early and aggressive control of cardiovascular risk factors is likely needed to reduce lifetime risk of CHD.
Diabetic Medicine 12/2011; 29(4):453-63. DOI:10.1111/j.1464-5491.2011.03542.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of type 2 diabetes mellitus (T2DM) is increasing in adolescents in most western countries. The time-course of glycemic control and impact of early treatment remain poorly understood.
To determine the change in incidence of T2DM, and the time-course of glycemic control in a regional pediatric cohort with T2DM.
Retrospective analysis of prospectively collected data on 52 patients with T2DM from a population-based treatment referral cohort from 1 January 1995 to 31 December 2007.
The annual incidence of new cases of T2DM in children <15 yr increased fivefold in the Auckland region of New Zealand from 1995 [0.5/100,000; 95% confidence interval (CI) 0.0–2.2] to 2007 (2.5/100,000; 95% CI 1.0–5.5). The average annual incidence per 100,000 over the entire period was 1.3 (95% CI 1.0–1.8) overall, 0.1 (0.0–0.4) in Europeans, and 3.4 in both Maori (2.0–5.3) and Pacifica (2.2–5.0). Fifty-seven percent of children were symptomatic at presentation. Fifty-eight percent of patients were treated with insulin from diagnosis, most of whom were symptomatic (p = 0.003). Follow-up data were available for 48 patients with a mean of 2.4 yr. Although insulin therapy was associated with a greater fall in HbA1c values in the first 12 months of treatment (to a nadir of 7.1 vs. 8.1%, p < 0.05), there was a rapid deterioration after 12 months, and subsequent mean HbA1c values were >9% in both groups. Therapy did not affect body mass index standard deviation score (BMI SDS).
The incidence of T2DM in childhood or adolescence increased markedly over a 13-yr period in the Auckland region. Long-
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