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Georgeanna Klingensmith

Publications and source records attributed to Georgeanna Klingensmith.

17 recordsLinked to original sources
PubMed2006

Prevalence of autoantibody-negative diabetes is not rare at all ages and increases with older age and obesity.

OBJECTIVE: A significant percentage of nonautoimmune forms of diabetes presents among children in all age groups, with a remarkable increase with age. DESIGN: From October 1992 to October 2004, a total of 859 children less than 18 yr of age were newly diagnosed with diabetes at the Barbara Davis Center for Childhood Diabetes and had blood samples obtained within 2 wk of disease onset for analysis of antiislet autoantibodies to glutamic acid decarboxylase-65, insulinoma-associated antigen-2, insulin, and islet cell autoantibodies. The relationship of autoantibody positivity with human leukocyte antigen (HLA) class II, body mass index (BMI), glycosylated hemoglobin, age, and ethnicity was analyzed. RESULTS: Overall 19% (159 of 859) of these children with newly diagnosed diabetes were negative for all autoantibodies, and autoantibody negativity was significantly increased with age (P < 0.01). The Hispanic and Black subjects had significantly increased autoantibody negativity among older children with higher BMI than White subjects. The patients with the highest risk HLA genotype, DR3-DQ2/DR4-DQ8, were significantly less autoantibody negative (P = 0.001), whereas the HLA-protective allele, DQB1*0602, was significantly increased among the autoantibody-negative patients (P < 0.0001). Insulin autoantibodies were dramatically age dependent and were inversely correlated with age in both prevalence (P < 0.0001) and levels (P < 0.0001). Autoantibody positivity was inversely correlated with both BMI and age using multivariate analysis (P < 0.0001 and P = 0.0078, respectively). CONCLUSIONS: A significant percentage of children newly diagnosed with diabetes are negative for all antiislet autoantibodies with a marked increase in obesity-associated autoantibody-negative diabetes after age 10, suggesting diabetes heterogeneity at all ages.

Adolescent↗
PubMed2006

Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY).

OBJECTIVE: The aim of this study was to assess the utility of hemoglobin A1c (HbA1c) measurements in the early detection of clinical type 1 diabetes during prospective follow-up of children with islet autoimmunity. METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) has followed for development of islet autoimmunity and diabetes general population newborns carrying human leukocyte antigen (HLA) genotypes conferring risk for type 1 diabetes and young siblings or offspring of people with type 1 diabetes. Testing for autoantibodies was performed at least once in 2234 and twice or more in 1887 children. Among the latter, 100 children tested positive on at least two consecutive visits. To date, 92 children have developed persistent islet autoantibodies to glutamic acid decarboxylase 65 (GAD65), insulin, or insulinoma associated antigen-2 (IA-2) and had at least two subsequent clinic visits. These children had study visits with point-of-care testing for HbA1c and random glucose every 3-6 months and those with random plasma glucose above 11.1 mmol/L or HbA1c above 6.3% were evaluated by a pediatric endocrinologist for clinical diabetes. RESULTS: During a mean follow-up of 3.4 yr from onset of autoimmunity, 28 children developed type 1 diabetes, at mean age of 6.5 yr. Mean prediagnostic HbA1c was 5.1% [standard deviation (SD) = 0.4%]. In a Cox regression model accounting for changes in values in individuals over time, increase in HbA1c predicted increased risk of progression to type 1 diabetes, hazard ratio = 4.8 (95% confidence interval 3.0-7.7) for each SD of 0.4%, independent of random glucose and number of autoantibodies. Increase in random plasma glucose levels only marginally predicted risk of progression (hazard ratio = 1.4, 95% confidence interval 1.02-1.8, per SD of 1.1 mmol/L). CONCLUSIONS: Normal but increasing Hb1Ac may be useful in early detection of type 1 diabetes, whereas random plasma glucose levels were less predictive.

Adolescent↗
PubMed2006

The use of insulin pumps with meal bolus alarms in children with type 1 diabetes to improve glycemic control.

OBJECTIVE: The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS: This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms. RESULTS: After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 +/- 3.7 to 2.5 +/- 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 +/- 2.7 to 4.2 +/- 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 +/- 1.12 to 8.86 +/- 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 +/- 1.04 to 8.67 +/- 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values. CONCLUSIONS: While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.

Adolescent↗
PubMed2005

Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase.

BACKGROUND: Nonalcoholic fatty liver disease, a cause of chronic liver disease in obese adults also occurs in obese children. In susceptible populations, fatty liver progresses to nonalcoholic steatohepatitis and eventually to fibrosis and cirrhosis. Nonalcoholic steatohepatitis is associated with elevation of alanine aminotransferase, although the aminotransferases can also be normal. The prevalence of nonalcoholic fatty liver disease in type 2 diabetes is unclear in adults and unknown in children. OBJECTIVES: The aim of this study was to estimate the prevalence of elevated serum aminotransferases as a marker of nonalcoholic fatty liver disease in pediatric type 2 diabetes and to identify correlates of aminotransferase elevation. METHODS: A chart review was completed on 115 children with type 2 diabetes at a pediatric diabetes clinic. The prevalence of elevated alanine aminotransferase was calculated from the 42% of patients with available aminotransferase measurements and correlations with fasting lipids, hemoglobin A-1c, body mass index, age and diabetes therapy were sought. RESULTS: The prevalence of elevated alanine aminotransferase was 48%. There was no association between elevations and other variables. Among subjects with elevated alanine aminotransferase, 39% were one to two times above normal, 26% were two to three times normal and 35% were greater than three times above normal. Several patients experienced improvement in aminotransferase elevations after using insulin-sensitizing medications. CONCLUSIONS: There is a high prevalence of elevated serum aminotransferases among children with type 2 diabetes unrelated to age, body mass index, glycemic control, blood lipids or diabetic therapy. The significance of this abnormality and its relationship to nonalcoholic fatty liver disease requires further evaluation.

Adolescent↗
PubMed2005

Use of insulin glargine in children under age 6 with type 1 diabetes.

AIM: Children under 6 yr have the highest incidence of severe hypoglycemia (SH) and the greatest likelihood of brain damage from SH. The purpose of this study is to evaluate the use of insulin glargine (Lantus in children under age 6 with type 1 diabetes (T1D). METHODS: The electronic medical records were reviewed for patients under age 6 during the first 6 months of insulin glargine therapy and compared with age, sex, and duration of diabetes for matched control patients on neutral protamine Hagedorn (NPH) insulin. Data from 128 subjects (32 male pairs and 32 female pairs) were collected relating to the incidence of severe and non-severe hypoglycemic events, hemoglobin A1c (HbA1c) values, body mass index (BMI), and daily insulin dose. Additionally, parents were asked to complete a diabetes Quality of Life (QoL) survey. RESULTS: In the 6 months before the study period, the glargine group had 16 SH events compared with three in the 6 months post-glargine. The comparison (NPH) group had seven and six SH events in their respective 6-month periods. Nighttime SH events in the glargine group decreased from 12 prestudy events to one during the study period. The average daily insulin dose in the glargine group was higher than that in the NPH group (0.8+/- 0.2 vs. 0.7+/- 0.2 U/kg/day; p=0.03). The HbA1c values, BMI, and QoL responses were not significantly different between the two groups. CONCLUSIONS: SH was decreased, particularly at night (from 12 episodes to one), after the introduction of glargine in young children with T1D.

Body Mass Index↗
PubMed2004

Redefining the clinical remission period in children with type 1 diabetes.

PURPOSE: To redefine the clinical remission period for different aged children receiving the current standard of diabetes care. METHODS: An electronic patient records system was used to identify 552 children newly diagnosed with type 1 diabetes (T1D) from 1997 to 2001 who had an initial hemoglobin A1c (HbA1c) value at the time of diagnosis and at least one other value measured in the ensuing year. The insulin dosage previously used to define the remission period [<0.5 units per kg body weight per day (U/kg/d)] was evaluated for the different aged children. RESULTS: The mean insulin dosages for all age groups were >0.5 U/kg/d by 9 months after diagnosis. The mean HbA1c values were above 8% by 6 months after diagnosis for the 6-9 and the 10-12 yr age groups and by 9 months after diagnosis for the >or=13 yr age group. The percentage of children <or=5 yr of age who continued to receive <0.5 U/kg/d of insulin was higher than for the other three age groups. However, this group did not achieve a mean HbA1c value <8% at any time. CONCLUSION: Older children have a longer remission period than younger children. The clinical definition of the remission period should be redefined to include both the insulin dose and the HbA1c level. Any attempt to extend the remission period in children is more apt to be successful in dealing with older children and with the introduction of the intervention as soon after diagnosis as is feasible.

Adolescent↗
PubMed2003

Timing of initial cereal exposure in infancy and risk of islet autoimmunity.

CONTEXT: Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM). OBJECTIVE: To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA). DESIGN: Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years. SETTING: Newborn screening for HLA was done at St Joseph's Hospital in Denver, Colo. First-degree relatives of type 1 DM individuals were recruited from the Denver metropolitan area. PARTICIPANTS: We enrolled 1183 children at increased type 1 DM risk, defined as either HLA genotype or having a first-degree relative with type 1 DM, at birth and followed them prospectively. We obtained exposure and outcome measures for 76% of enrolled children. Participants had variable lengths of follow-up (9 months to 9 years). MAIN OUTCOME MEASURES: Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter. Children with IA (n = 34) were defined as those testing positive for at least 1 of the autoantibodies on 2 or more consecutive visits and who tested positive or had diabetes on their most recent visit. RESULTS: Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age. In children who were positive for the HLA-DRB1*03/04,DQB8 genotype, adjusted HRs were 5.55 (95% CI, 1.92-16.03) and 12.53 (95% CI, 3.19-49.23) for initial cereal exposure between ages 0 to 3 months and at 7 months or older, respectively. CONCLUSION: There may be a window of exposure to cereals in infancy outside which initial exposure increases IA risk in susceptible children.

Animals↗
PubMed2003

Reduced hypoglycemic episodes and improved glycemic control in children with type 1 diabetes using insulin glargine and neutral protamine Hagedorn insulin.

OBJECTIVE: The purpose of this study was to evaluate the use of a new long-acting basal insulin, insulin glargine (IG), in children with type 1 diabetes. Study design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60 girls), were collected for 9 months before and 9 months after IG treatment. During IG therapy, all subjects received morning neutral protamine Hagedorn insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage. The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values, body weight, and daily insulin dose were recorded at each clinic visit. RESULTS: The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced from a total of 22 in the 9 months before IG to nine in the 9 months after IG. Severe nocturnal events were similarly reduced from 14 to four episodes. The mean (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3 months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months (P=.01). CONCLUSION: Insulin glargine therapy can reduce hypoglycemic episodes in children and adolescents with suboptimal glucose control without jeopardizing glycemic control.

Adolescent↗
PubMed2003

Use of the GlucoWatch biographer in children with type 1 diabetes.

OBJECTIVE: To determine whether use of the GlucoWatch biographer improves glucose control in children and adolescents with type 1 diabetes. METHODS: Forty children in poor glucose control (glycohemoglobin [HbA1c] >8%) were randomized to diabetes management with or without glucose monitoring using the biographer. Conventional glucose monitoring was performed 4 times daily in both groups. Those randomized to the biographer group were asked to wear the device 4 times per week for 3 months (intervention phase) and to perform blood glucose monitoring if the biographer alerted them that glucose was < or =70 mg/dL (3.9 mmol/L) or > or =300 mg/dL (16.7 mmol/L). After 3 months, all patients received biographers and were followed for 6 months (observation phase). HbA1c values were determined at baseline and after 1, 3, 6, and 9 months. RESULTS: The median HbA1c was 8.6% and 8.9% (control versus biographer) at baseline and was significantly lower in the biographer group after 3 months (8.4% vs 9%). More hypoglycemia was detected when subjects were wearing the biographer, especially at night. No severe hypoglycemia occurred. During the observation phase, HbA1c values at 6 months were 8.5% and 8.3% and at 9 months were 8.6% and 8.4% in the control and biographer groups, respectively. Two children dropped out of the study, 1 because of skin irritation from using the device. CONCLUSIONS: The GlucoWatch biographer was well tolerated by children and adolescents and significantly improved glucose control compared with standard therapy. The use of the biographer with an alarm to detect nocturnal hypoglycemia has the potential to increase the safety of diabetes management in children.

Adolescent↗
PubMed2003

Symptoms of common maternal infections in pregnancy and risk of islet autoimmunity in early childhood.

OBJECTIVE: The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age <or=15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3-15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD(65), insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity. RESULTS: Children whose mother reported at least one symptom of infection during pregnancy (mostly respiratory or gastrointestinal) had a significantly lower risk of islet autoimmunity compared with other children (hazard ratio 0.48; 95% CI 0.27-0.83). After stratification, the association appeared among girls (0.21; 0.09-0.48) but not among boys (1.09; 0.47-2.51) with a P value for interaction of 0.005. Symptoms of neonatal infections, early daycare attendance, exposure to cats or dogs, and household crowding were not related to islet autoimmunity. CONCLUSIONS: Symptoms of maternal infections in pregnancy predicted a significantly lower risk of islet autoimmunity in young girls, suggesting a protective effect of such infections.

Diabetes Mellitus, Type 1↗
PubMed2002

Predictors of acute complications in children with type 1 diabetes.

CONTEXT: Diabetic ketoacidosis and severe hypoglycemia are acute complications of type 1 diabetes that are related, respectively, to insufficient or excessive insulin treatment. However, little is known about additional modifiable risk factors. OBJECTIVE: To examine the incidence of ketoacidosis and severe hypoglycemia in children with diabetes and to determine the factors that predict these complications. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 1243 children from infancy to age 19 years with type 1 diabetes who resided in the Denver, Colo, metropolitan area were followed up prospectively for 3994 person-years from January 1, 1996, through December 31, 2000. MAIN OUTCOME MEASURES: Incidence of ketoacidosis leading to hospital admission or emergency department visit and severe hypoglycemia (loss of consciousness, seizure, or hospital admission or emergency department visit). RESULTS: The incidence of ketoacidosis was 8 per 100 person-years and increased with age in girls (4 per 100 person-years in < 7; 8 in 7-12; and 12 in > or =13 years; P<.001 for trend). In multivariate analyses, sex-adjusted and stratified by age (<13 vs > or =13 years), the risk of ketoacidosis in younger children increased with higher hemoglobin A(1c) (HbA(1c)) (relative risk [RR], 1.68 per 1% increase; 95% confidence interval [CI], 1.45-1.94) and higher reported insulin dose (RR, 1.40 per 0.2 U/kg per day; 95% CI, 1.20-1.64). In older children, the risk of ketoacidosis increased with higher HbA(1c) (RR, 1.43; 95% CI, 1.30-1.58), higher reported insulin dose (RR, 1.13; 95% CI, 1.02-1.25), underinsurance (RR, 2.18; 95% CI, 1.65-2.95), and presence of psychiatric disorders (for boys, RR, 1.59; 95% CI, 0.96-2.65; for girls, RR, 3.22; 95% CI, 2.25-4.61). The incidence of severe hypoglycemia was 19 per 100 person-years (P<.001 for trend) and decreased with age in girls (24 per 100 patient-years in < 7, 19 in 7-12, and 14 in > or =13 years). In younger children, the risk of severe hypoglycemia increased with diabetes duration (RR, 1.39 per 5 years; 95% CI, 1.16-1.69) and underinsurance (RR, 1.33; 95% CI, 1.08-1.65). In older children, the risk of severe hypoglycemia increased with duration (RR, 1.34; 95% CI, 1.25-1.51), underinsurance (RR, 1.42; 95% CI, 1.11-1.81), lower HbA(1c) (RR, 1.22; 95% CI, 1.12-1.32), and presence of psychiatric disorders (RR, 1.56; 95% CI, 1.23-1.98). Eighty percent of episodes occurred among the 20% of children who had recurrent events. CONCLUSIONS: Some children with diabetes remain at high risk for ketoacidosis and severe hypoglycemia. Age- and sex-specific incidence patterns suggest that ketoacidosis is a challenge in adolescent girls while severe hypoglycemia continues to affect disproportionally the youngest patients and boys of all ages. The pattern of modifiable risk factors indicates that underinsured children and those with psychiatric disorders or at the extremes of the HbA(1c) distribution should be targeted for specific interventions.

Acute Disease↗
PubMed2002

Millennium award recipient contribution. Identification of children with early onset and high incidence of anti-islet autoantibodies.

A total of 21,000 general population newborns (NECs) and 693 young siblings-offspring of patients with type 1A diabetes (SOCs) were class II genotyped and 293 NECs and 72 SOCs with the high-risk genotype, DR3/4, DQB1*0302 have been prospectively evaluated. Seventeen individuals who converted to persistent autoantibody positivity and two autoantibody-negative control groups (35 SOCs and 24 NECs) were typed for HLA-A class I alleles. The A1, A2 genotype was significantly increased among the autoantibody-positive subjects (47%) compared to autoantibody-negative SOCs (14%, P = 0.01) and NECs (13%, P = 0.02). Life-table analysis of DR3/4, DQB1*0302 siblings revealed a risk of 75% for development of islet autoantibodies by the age of 2 years for those with A1, A2. The HLA-A2 phenotype frequency was increased among an independent DR3/4, DQB1*0302 young diabetes cohort (64% versus 33% for autoantibody-negative NECs). These results suggest that a high incidence and early appearance of islet autoantibodies for siblings of patients with type 1A diabetes are associated with DR3/4, DQB1*0302 and potentially increased with HLA-A genotype A1, A2.

Adolescent↗