Georgeanna J. Klingensmith

Type 2 diabetes in children and adolescents

Arlen L. Rosenblooma, Janet H. Silversteinb, Shin Amemiyac, Phil Zeitlerd and Georgeanna J Klingensmithe abDivision of Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; cDivision of Endocrinology, Department of Pediatrics, Saitama Medical University, Saitama, Japan; dDivision of Endocrinology, Department of Pediatrics, The Children’s Hospital, University of Colorado Denver, Aurora, CO, USA; eDepartment of Pediatrics, The Children’s Hospital and Barbara Davis Center, University of Colorado Denver, Aurora, CO, USA. Corresponding author: Professor Emeritus Arlen L Rosenbloom Division of Endocrinology Department of Pediatrics, University of Florida College of Medicine, 1701 SW 16th Avenue Gainesville, FL 32608 USA. e-mail: rosenal@peds.ufl.edu

Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY)

SummaryAutoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown environmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been established using a simple and rapid cord blood screening for HLA alleles. The DRB1 and DQB1 second exon sequences were co-amplified using the polymerase chain reaction and hybridized with single and pooled sequence-specific oligonucleotide probes. Four individual probes were used to detect the susceptibility alleles DRB1*03, DRB1*04, and DQBl*0302 as well as the usually protective DRB1*15/16 (DR2) alleles. In addition, pooled probes allow the distinction of DR3/3 from the DR3/x genotype (where x is neither DR2, 3, nor 4) and DR4/4 from DR4/x. Among 5000 newborns from the general Denver population, we have found the high-risk genotype (DRBl*03/ DRB1*04, DQBl*0302) to be present in 2.4% of non-Hispanic whites, 2.8% of Hispanics, and 1.6% of African Americans. The moderate-risk genotypes (DRB1*04, DQBl*0302/DRBl*04, DQB1*0302, DRB1*04, DQBl*0302/x, or DRBl*03/DRBl*03) are present in 17 % of American non-Hispanic whites, 24% of Hispanics and in 10% of African Americans. These results demonstrate the feasibility of a large-scale newborn screening for genes associated with IDDM. The ultimate role for such a screening in future routine prediction and prevention of IDDM will depend on the availability of an effective and acceptable form of clinical intervention.

Assessment and monitoring of glycemic control in children and adolescents with diabetes

Marian J Rewersa, Kuben Pillayb, Carine de Beaufortc, Maria E Craigd, Ragnar Hanase, Carlo L Acerinif and David M Maahsa aBarbara Davis Center, University of Colorado Denver, Aurora, CO, USA; bWestville Hospital, Durban, South Africa; cDECCP, Clinique Pediatrique/CHL, Luxembourg, Luxembourg; dInstitute of Endocrinology and Diabetes, Westmead, Australia; eDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden and fDepartment of Pediatrics, University of Cambridge, Cambridge, UK

Glycemic control in youth with diabetes: the SEARCH for diabetes in Youth Study.

OBJECTIVE To assess correlates of glycemic control in a diverse population of children and youth with diabetes. STUDY DESIGN This was a cross-sectional analysis of data from a 6-center US study of diabetes in youth, including 3947 individuals with type 1 diabetes (T1D) and 552 with type 2 diabetes (T2D), using hemoglobin A(1c) (HbA(1c)) levels to assess glycemic control. RESULTS HbA(1c) levels reflecting poor glycemic control (HbA(1c) >or= 9.5%) were found in 17% of youth with T1D and in 27% of those with T2D. African-American, American Indian, Hispanic, and Asian/Pacific Islander youth with T1D were significantly more likely to have higher HbA(1c) levels compared with non-Hispanic white youth (with respective rates for poor glycemic control of 36%, 52%, 27%, and 26% vs 12%). Similarly poor control in these 4 racial/ethnic groups was found in youth with T2D. Longer duration of diabetes was significantly associated with poorer glycemic control in youth with T1D and T2D. CONCLUSIONS The high percentage of US youth with HbA(1c) levels above the target value and with poor glycemic control indicates an urgent need for effective treatment strategies to improve metabolic status in youth with diabetes.

Prevalence and Correlates of Depressed Mood Among Youth With Diabetes: The SEARCH for Diabetes in Youth Study

OBJECTIVE.The objective of this study was to determine if depressed mood among youth with diabetes was associated with type and duration of diabetes, mean glycosylated hemoglobin (HbA1c) level, and the frequency of diabetic ketoacidosis (DKA) and hypoglycemic episodes, hospitalizations, and emergency department (ED) visits. METHODS.A total of 2672 youth (aged 10–21 years) who had diabetes for a mean duration of 5 years completed a SEARCH study visit, in which their HbA1c was measured and information about their demographic characteristics, diabetes type and duration, and episodes of DKA, hypoglycemia, hospitalizations, and ED visits over the previous 6 months was collected. Their level of depressed mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS.Among these youth, 14% had mildly (CES-D 16–23) and 8.6% had moderately or severely (CES-D ≥24) depressed mood. Females had a higher mean CES-D score than males. After adjusting for demographic factors, and duration of diabetes, we found the prevalence of depressed mood to be higher among males with type 2 diabetes than those with type 1 diabetes and to be higher among females with comorbidities than those without comorbidities. Higher mean HbA1c and frequency of ED visits were associated with depressed mood. The prevalence of depressed mood among youth with diabetes was similar to that of published estimates of depressed mood among youth without diabetes. CONCLUSIONS.Physicians and other health care professionals should consider screening youth with diabetes for depressed mood in clinical settings, particularly youth with poor glycemic control, those with a history of frequent ED visits, males with type 2 diabetes, and females with comorbidities.

Presence of Diabetic Ketoacidosis at Diagnosis of Diabetes Mellitus in Youth: The Search for Diabetes in Youth Study

OBJECTIVE. The purpose of this work was to determine the prevalence and predictors of diabetic ketoacidosis at the diagnosis of diabetes in a large sample of youth from the US population. PATIENTS AND METHODS. The Search for Diabetes in Youth Study, a multicenter, population-based registry of diabetes with diagnosis before 20 years of age, identified 3666 patients with new onset of diabetes in the study areas in 2002–2004. Medical charts were reviewed in 2824 (77%) of the patients in a standard manner to abstract the results of laboratory tests and to ascertain diabetic ketoacidosis at the time of diagnosis. Diabetic ketoacidosis was defined by blood bicarbonate <15 mmol/L and/or venous pH < 7.25 (arterial/capillary pH < 7.30), International Classification of Diseases, Ninth Revision, code 250.1, or listing of diabetic ketoacidosis in the medical chart. RESULTS. More than half (54%) of the patients were hospitalized at diagnosis, including 93% of those with diabetic ketoacidosis and 41% without diabetic ketoacidosis. The prevalence of diabetic ketoacidosis at the diagnosis was 25.5%. The prevalence decreased with age from 37.3% in children aged 0 to 4 years to 14.7% in those aged 15 to 19 years. Diabetic ketoacidosis prevalence was significantly higher in patients with type 1 (29.4%) rather than in those with type 2 diabetes (9.7%). After adjusting for the effects of center, age, gender, race or ethnicity, diabetes type, and family history of diabetes, diabetic ketoacidosis at diagnosis was associated with lower family income, less desirable health insurance coverage, and lower parental education. CONCLUSION. At the time of diagnosis, 1 in 4 youth presents with diabetic ketoacidosis. Those with diabetic ketoacidosis were more likely to be hospitalized. Diabetic ketoacidosis was a presenting feature of <10% of youth with type 2. Young and poor children are disproportionately affected.

Early Exposure to Cow's Milk and Solid Foods in Infancy, Genetic Predisposition, and Risk of IDDM

Using a case-control study design, we examined the hypothesis that early exposure to cows milk and solid foods increased the risk of IDDM. An infant diet history was collected from 164 IDDM subjects from the Colorado IDDM Registry with a mean birth year of 1973, and 145 nondiabetic population control subjects who were frequency matched to diabetic subjects on age, sex, and ethnicity. Early exposure was defined as exposure occurring before 3 mo of age. After controlling for ethnicity, birth order, and family income, more diabetic subjects were exposed early to cows milk (OR 4.5, 95% Cl 0.9–21.4) and solid foods (OR 2.5, Cl 1.4–4.3) than control subjects. To examine this association while accounting for the genetic susceptibility to IDDM, we defined individuals as high and low risk by an HLA-DQB1 molecular marker. Early exposure to cows milk was not associated with elevated risk for IDDM in low-risk individuals. Relative to unexposed low-risk individuals, early exposure to cows milk was strongly associated in individuals with a high risk marker (OR 11.3, Cl 1.2–102.0). Similar findings were observed for early exposure to solid foods. These data indicate that early exposure to cows milk and solid foods may be associated with increased risk of IDDM. The inclusion of HLA-encoded risk in the analyses demonstrates the combined effect of genetic and environmental factors.

Enterovirus Infection and Progression From Islet Autoimmunity to Type 1 Diabetes: The Diabetes and Autoimmunity Study in the Young (DAISY)

OBJECTIVE To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95–25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. CONCLUSIONS This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.

Assessment and management of hypoglycemia in children and adolescents with diabetes

Barbara Davis Center, University of Colorado at Denver,Aurora, CO, USACorresponding author:William Clarke, MDDepartment of PediatricsUniversity of VirginiaP.O. Box 800386CharlottesvilleVA 22908USA.Tel: 434 924 5897fax: 434 924 9181e-mail: wlc@virginia.eduEditors of the ISPAD Clinical Practice Consensus Guidelines2006–2007: William Clarke, Timothy Jones, Arleta Rewers,David Dunger, and Georgeanna J Klingensmith.

Transition From Pediatric to Adult Care for Youth Diagnosed With Type 1 Diabetes in Adolescence

OBJECTIVE: Youth with type 1 diabetes mellitus are at risk for poor glycemic control as they age into adulthood. The aim of this study was to describe sociodemographic and clinical correlates of poor glycemic control associated with the transfer of care from pediatric to adult diabetes providers among a cohort of youth with type 1 diabetes diagnosed in adolescence. METHODS: Analyses included 185 adolescent participants with recently diagnosed type 1 diabetes in the SEARCH for Diabetes in Youth Study with pediatric care at baseline who were age ≥18 years at follow-up. Demographic and clinical factors were measured by survey and laboratory results. Survival analysis was used to estimate the age of transition. Logistic regression analysis assessed the association of demographic and clinical factors with the transition of care and poor glycemic control at follow-up. RESULTS: Fifty-seven percent of participants had transitioned to adult diabetes care providers by the follow-up visit. The estimated median age of transition of care was 20.1 years (95% confidence interval 19.8–20.4). Older age, lower baseline glycosylated hemoglobin, and less parental education were independently associated with increased odds of transition. The odds of poor glycemic control at follow-up were 2.5 times higher for participants who transitioned to adult care compared with those who remained in pediatric care. CONCLUSIONS: Transferring from pediatric to adult care, experienced by more than half the sample, was associated with an increased risk of poor glycemic control at follow-up. These findings suggest that young adults need additional support when moving to adult care.