The interrelationships of glycemic control measures: HbA1c, glycated albumin, fructosamine, 1,5-anhydroglucitrol, and continuous glucose monitoring

Beck R, Steffes M, Xing D, Ruedy K, Mauras N, Wilson DM, Kollman C, the Diabetes Research in Children Network (DirecNet) Study Group. The interrelationships of glycemic control measures: HbA1c, glycated albumin, fructosamine, 1,5‐anhydroglucitrol, and continuous glucose monitoring. Objectives: To describe the interrelationships of glycemic control measures: hemoglobin A1c (HbA1c), glycated albumin, fructosamine, 1,5‐anhydroglucitrol (1,5‐AG), and continuous glucose monitoring (CGM) in children and adolescents with type 1 diabetes. Methods: In total, 26 subjects of age 4–17 had HbA1c measurement followed within 14 d by three laboratory measures of glycemia and the collection of CGM glucose data (N = 21). Results: Glycated albumin and fructosamine levels had a higher correlation with each other than with HbA1c. The correlation of 1,5‐AG with HbA1c was lower (absolute r value = 0.25). All four measures had a similar degree of correlation with CGM‐measured mean glucose (absolute r value = 0.50–0.56) and with hyperglycemic area under the curve (AUC) at 180 mg/dL (0.50–0.60). Conclusion: Each of the four measures (i.e., HbA1c, glycated albumin, fructosamine, and 1,5‐AG) had a similar correlation with mean glucose and hyperglycemic AUC‐180. 1,5‐AG did not correlate with hyperglycemic AUC‐180 better than did HbA1c.     

Hemoglobin A1c and fructosamine correlate in a patient with sickle cell disease and diabetes on chronic transfusion therapy

In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A_1c (HbA_1c) is unreliable and the American Diabetes Association recommends monitoring long‐term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA_1c. We present a case of a patient with SCD and cystic fibrosis‐related diabetes on monthly chronic transfusions therapy (CTT) who had well‐correlated “steady state” HbA_1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long‐term glycemic control in patients with SCD on CTT programs.     

Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus

BACKGROUND: The relationship between hemoglobin A1c (HbA1c) and iron status in type 1 diabetes mellitus (DM) has not been adequately studied. In this prospective investigation, we aimed to determine the effect of iron deficiency on HbA1c in diabetic patients who also had insufficient iron stores. METHODS: Thirty-seven patients with type 1 DM were included in the study. Eleven of them were also iron deficient (ID) and the remaining 26 were iron-sufficient (IS). Two non-diabetic control groups were selected for the ID and IS groups. All patients with ID were treated with iron at 6 mg/kg per day for 3 months. Glycemia in diabetic patients was monitored at home before breakfast and supper by a glycometer. Hemoglobin A1c was measured in all subjects at the beginning and the end of the study. RESULTS: Patients with ID DM had higher levels of HbA1c than those in the control group (P < 0.001). There were no significant differences in the weekly average glucose concentration of the patients with ID DM before and after iron supplementation. In contrast, HbA1c decreased from a mean of 10.1 +/- 2.7% to a mean of 8.2 +/- 3.1% (P < 0.05). Additionally, HbA1c in ID non-diabetic patients decreased from a mean of 7.6 +/- 2.6% to 6.2 +/- 1.4% after iron therapy (P < 0.05). CONCLUSIONS: We conclude that among type 1 DM patients with similar level of glycemia, iron deficiency anemia is associated with higher concentrations of HbA1c. In addition, iron replacement therapy leads to a drop in HbA1c in both diabetic and non-diabetic patients. The iron status of the patient must be considered during the interpretation of HbA1c concentrations in type 1 DM.     

Hemoglobin A1c is a reliable criterion for diagnosing type 1 diabetes in childhood and adolescence

Ehehalt S, Gauger N, Blumenstock G, Feldhahn L, Scheffner T, Schweizer R, Neu A for the DIARY‐Group Baden‐Wuerttemberg. Hemoglobin A1c is a reliable criterion for diagnosing type 1 diabetes in childhood and adolescence. Background: Little is known about the use of the hemoglobin A1C (HbA1c) test for the diagnosis of diabetes in childhood and adolescence. The aim is to investigate sensitivity and specificity of HbA1c at onset of childhood type 1 diabetes. Methods: A total of 184 children and adolescents with blood glucose levels above 200 mg/dL (11.1 mmol/L) were included: 84.8% (n = 156, mean age 9.0 yr) with new onset of type 1 diabetes, 15.2% (n = 28, mean age 6.1 yr) with transient hyperglycemia. HbA1c was measured using the Bayer^® DCA2000 analyzer. Results: Patients with new onset of type 1 diabetes (n = 156) had HbA1c values between 6.6% and > 14% (mean (SD) 11.4 (2.0)%; IQR, interquartile range 9.8–13.3%). All patients suffered from typical symptoms of hyperglycemia, i.e., polyuria and polydipsia. In the patient group with transient hyperglycemia (n = 28), HbA1c values were between 4.5 and 6.1% (mean (SD) 5.3 (0.4)%; IQR 5.0–5.6%). None of these patients reported typical symptoms of diabetes. All patients with HbA1c values greater than 6.35% had new onset of type 1 diabetes. Sensitivity of HbA1c at the onset of childhood type 1 diabetes was calculated to be 100%. In patients with HbA1c values less than 6.35%, the diagnosis of type 1 diabetes could be excluded. Thus, specificity of HbA1c as diagnostic criterion was 100%. Conclusions: Childhood type 1 diabetes can be diagnosed and excluded with high reliability by means of HbA1c testing.     

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

BACKGROUND: Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. METHODS: Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. RESULTS: The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. CONCLUSIONS: T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.     

Predictors of glucose control in children and adolescents with type 1 diabetes mellitus

AIMS: To evaluate the glucose control [(as measured by hemoglobin A1c (HbA1c)], the factors associated with glycemic control, and possible explanations for these associations in a sample of children and adolescents with type 1 diabetes. METHODS: Data were collected on 155 children and adolescents, with type 1 diabetes mellitus, attending a multidisciplinary diabetes clinic in Portland, OR. Patients' hospital charts were reviewed to determine demographic factors, disease-related characteristics, and HbA1c level. RESULTS: Mean percent HbA1c was 9.3. Adolescents between the ages of 14 and 18 yr were in poorer metabolic control (adjusted mean percent HbA1c 0.56 higher than children 2-8 yr). Children who attended the clinic three to four times in the previous year were in better control (adjusted mean percent HbA1c 0.46 lower than those who visited two or fewer times and 1.11 lower than those who attended five or more times). Children with married parents were in better glycemic control than those of single, separated, or divorced parents (adjusted mean percent HbA1c 0.47 lower for children of married parents). This effect appeared to be mediated, in part, by the number of glucose checks performed per day. CONCLUSIONS: This study suggests that adolescents should be targeted for improved metabolic control. Diabetes team members need to be aware of changing family situations and provide extra support during stressful times. Regular clinic attendance is an important component of intensive diabetes management. Strategies must be developed to improve accessibility to the clinic and to identify patients who frequently miss appointments.     

Initiation of insulin glargine in children and adolescents with type 1 diabetes

BACKGROUND: Glargine (Lantus) is a recently approved, long-acting insulin analog that is increasingly being used in children with diabetes. The aim of this retrospective chart review was to summarize our experience in starting glargine in children and adolescents with diabetes. SUBJECTS AND STUDY METHODS: We reviewed the medical records of 71 children with type 1 diabetes (29 boys and 42 girls) who initiated glargine therapy to improve glycemic control between 1 June 2001 and 30 June 2002. Data were collected for 6 months before and 6 months after adding glargine. RESULTS: Subjects' mean age [+/-standard deviation (SD)] at diagnosis of diabetes was 7.5 +/- 4.1 yr. Mean age at initiation of glargine therapy was 11.5 +/- 4.9 yr. The total daily long-acting insulin dose decreased by about 20% after initiating glargine therapy. There were no significant differences in hemoglobin A1c (HbA1c) and blood glucose control prior to and after initiating glargine therapy (HbA1c at baseline 8.9 +/- 1.6% and HbA1c after 6 months of glargine therapy was 8.9 +/- 1.5%). Overall, blood glucose concentrations did not differ significantly throughout the study. Patients who switched to glargine because of nocturnal hypoglycemia had a 65% decrease in nocturnal blood glucose reading less than 50 mg/dL. There were three seizures in the first week after initiating glargine therapy. CONCLUSION: This retrospective study suggests that glargine is at least as effective as other long-acting insulins but that care must be taken during the conversion process to avoid hypoglycemia.