The case for biennial retinopathy screening in children and adolescents

OBJECTIVE: Current guidelines recommend annual retinopathy screening 2 years after onset (for pubertal-onset type 1 diabetes) and after 5 years (or age 11, whichever is earlier) for prepubertal onset. Our aim was to describe the natural history of retinopathy and to explore optimal retinal screening intervals for children and adolescents (aged <20 years) screened according to these guidelines. RESEARCH DESIGN AND METHODS: More than 1,000 children and adolescents, followed longitudinally, were screened for retinopathy using seven-field stereoscopic fundus photography through dilated pupils. Of these, 668 had baseline and follow-up retinal screening. Using generalized estimating equations, we compared the risk of retinopathy with baselines at yearly intervals, in older and younger groups, in higher risk groups (diabetes duration >10 years or HbA(1c) >10% at any screening), and after stratification 10% recorded at any visit, retinopathy increased significantly after 2 years (P = 0.001) but not until 3 years in the group whose HbA(1c) was always 2 years later. Individuals with especially poor control, duration >10 years, or significant retinopathy should be screened more frequently.     

Blood pressure does not rise before the onset of microalbuminuria in children followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study Group

OBJECTIVE: To examine whether a rise in blood pressure could be detected before the onset of microalbuminuria (MA) in a cohort of children followed from diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: The Oxford Regional Prospective Study is an incident cohort study of children with type 1 diabetes aged (mean +/- SD) 9.8 +/- 3.7 years at diagnosis. Subjects were assessed annually from diagnosis, with measurement of HbA1c, arterial blood pressure (random zero), and three urine samples for estimation of the albumin/creatinine ratio. During follow-up, 63 of 494 children developed MA at one or more annual assessments and were designated as cases for a nested case-control study. Each case was matched for sex and age at diagnosis with two normoalbuminuric control subjects. Blood pressure (BP) data were compared at corresponding years of diabetes duration. RESULTS: Cases with MA were similar to normoalbuminuric control subjects with respect to age and BMI, but they had higher mean HbA1c levels (mean difference 1.1%, P < 0.001). In the years before the onset of MA, the diastolic BP standard deviation score (SDS) was significantly higher than zero in cases (mean 0.49, P < 0.001) and in control subjects (0.50, P < 0.001). No difference could be detected between cases and control subjects before the onset of MA in either systolic or diastolic BP (mean difference systolic -1.2 mmHg [95% CI -4.7 to 2.7], mean difference diastolic 0.1 mmHg [-2.4 to 2.6]). However, within the cases, the onset of MA was associated with elevations in systolic and diastolic BP SDSs (F = 16.1, P < 0.001; and F = 18.0, P < 0.001). BMI, but not HbA1c, was associated with systolic and diastolic BP SDSs in the subjects with MA (F = 0.6, P = 0.4; and F = 12.3, P = 0.001). However, the association of BP with MA remained signifcant for systolic BP (P = 0.001) and for diastolic BP (P < 0.001) after adjusting for BMI. CONCLUSIONS: A rise in systemic BP cannot be detected before the first appearance of MA in children with type 1 diabetes. BP rises concurrently with the onset of MA and is also closely related to BMI.     

Glycemic control with insulin glargine as part of an ethnically diverse, community-based diabetes management program

OBJECTIVE: To evaluate the contribution of long-acting basal insulin therapy (insulin glargine) to glycemic control in a predominantly Hispanic population participating in a community-based diabetes management program, Project Dulce. RESEARCH DESIGN AND METHODS: This retrospective analysis included 3122 adult patients with diabetes from 17 community clinics in San Diego County, California who participated in Project Dulce between July 2000 and March 2003. A subset of 180 patients received insulin glargine because of ongoing, inadequate glycemic control (ie, elevated HbA1c). Glycemic control was evaluated by mean adjusted HbA1c during follow-up clinical visits using hierarchical linear modeling, with values determined separately before and after initiation of insulin glargine. RESULTS: At baseline, the mean number of individuals with hypoglycemia, presence of diabetic complications, and duration of diabetes were greater in the glargine group that in the reference group. HbA1c at baseline was 8.79 and 9.44 (P = 0.019) in the reference and glargine groups, respectively. Mean adjusted HbA1c in the glargine group was 8.80 at baseline, 7.89 before initiation of insulin glargine (P < 0.001 vs baseline), and 7.34 after adding insulin glargine (P < 0.001 vs pre-glargine). In the reference group, mean adjusted HbA1c decreased from 8.81 at baseline to 7.40 during follow-up (P < 0.001 vs baseline). CONCLUSIONS: A comprehensive program of diabetes care in Project Dulce improved HbA1c significantly in a predominantly Hispanic population. Adding long-acting basal insulin therapy with insulin glargine produced significant incremental improvement in HbA1c.     

Antidiabetic prescriptions and glycemic control in German patients with type 2 diabetes mellitus: a retrospective database study

OBJECTIVES: This study examined patterns of antidiabetic treatment among individuals with type 2 diabetes in Germany and investigated potential differences in attainment of glycemic control associated with the use of specific antidiabetic regimens. METHODS: This was a retrospective database study. Data were obtained from the German IMS Disease Analyzer-MediPlus database. Patients aged >or=20 years who were identified as having type 2 diabetes and who underwent glycosylated hemoglobin (HbA(1c)) testing at least once between April 1, 2004, and December 31, 2004, were included in the analyses. Potential associations between age, sex, and diabetic complications and the use of specific antidiabetic medications were examined. Also examined were potential associations between attainment of the HbA(1c) target for glycemic control (56.5%), particular patient characteristics, and the use of specific antidiabetic medications. RESULTS: The study included data from 5135 patients with type 2 diabetes (mean age, 67 years; 2702 men, 2433 women; mean [SD] HbA(1c), 6.9% [1.2%]). The most commonly diagnosed comorbidities were hypertension (66.5%) and obesity (18.7%). There were no significant differences in mean age, sex, or comorbidities between patients categorized by HbA(1c) values 6.5%. The most commonly prescribed antidiabetic medications were metformin (20.4%), a sulfonylurea (11.7%), and oral combination therapy (10.9%). In the assessment of potential associations between selected patient characteristics and the receipt of specific antidiabetic medications, individuals were less likely to receive metformin monotherapy if they were aged >or=75 years (12.0%, compared with 21.4% of those aged 65-74 years and 24.7% of those aged <65 years; P < 0.001) or had a diagnosis of a diabetic complication (15.9%, compared with 21.2% in those without complications; P < 0.001). Among those who were more likely to receive insulin monotherapy were women (11.5%, compared with 9.6% of men; P = 0.025) and patients with diabetic complications (13.9%, compared with 9.8% of those without complications; P < 0.001). More than half (52.7%) of patients did not attain the HbA(1c) target. There were significant differences between patients attaining the HbA(1c) target and receipt of specific antidiabetic medications (P < 0.001). Patients treated with insulin monotherapy or oral plus insulin combination therapy were least likely to reach the HbA(1c) target (26.4% and 22.9%, respectively, attained glycemic control; both, P < 0.001). Only 179 (31.9%) of 562 patients treated with oral combination therapy achieved the HbA(1c) target (P < 0.001). CONCLUSIONS: Over half of these German patients with type 2 diabetes failed to attain the HbA(1c) target for glycemic control. Patients who were prescribed insulin monotherapy or combination therapy were least likely to achieve the target.     

Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.

OBJECTIVE: Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10-16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels > or =7.0 and < or =13.3 mmol/l (> or =126 and < or =240 mg/dl), HbA(1c) > or =7.0%, stimulated C-peptide > or =0.5 nmol/l (> or =1.5 ng/ml), and a BMI > 50th percentile for age. RESULTS: Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was -2.4 mmol/l (-42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA(1c) values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin. CONCLUSION: Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.     

Impact of diabetes screening on quality of life

OBJECTIVE: Diagnosis of a chronic illness can have a negative impact on patients' perception of their well-being ("labeling" effect). We sought to determine the effects of a new diagnosis of diabetes, discovered by systematic screening, on patients' health-related quality of life (HRQoL) 1 year after diagnosis. RESEARCH DESIGN AND METHODS: We performed diabetes screening at the Durham Veterans Affairs Medical Center of 1,253 outpatients, aged 45-64 years, who did not report having diabetes. Our initial screen was a serum HbA(1c) measurement. All subjects with HbA(1c) > or = 6.0% were invited for follow-up measurement of blood pressure and fasting plasma glucose. A case of unrecognized diabetes was defined as HbA(1c) > or = 7.0% or fasting plasma glucose > or = 7 mmol/dl. HRQoL was measured by Medical Outcomes Study Short Form 36 (SF-36) for all patients at baseline and 1 year after enrollment. Linear multivariable models were used to determine the independent effect of the new diagnosis of diabetes on HRQoL. RESULTS: Mean SF-36 Physical Component Score (PCS) for all patients was 36.2, and mean Mental Component Score (MCS) was 49.6. A total of 56 patients (4.5%) were found to have diabetes at screening. Patients found to have diabetes at screening had mean PCS of 35.6, which was not different from a mean PCS of 36.3 for those patients found not to have diabetes (P = 0.67). After adjusting for baseline PCS values, PCS 1 year after screening was similar for patients with and without diabetes found at screening (P = 0.95). Similarly, patients found to have diabetes at screening had mean MCS of 48.8; those found not to have diabetes had MCS of 49.6 (P = 0.70). After adjusting for baseline MCS values, MCS 1 year after screening was also similar between the two groups (P = 0.77). CONCLUSIONS: For patients with a new diagnosis of diabetes discovered through systematic screening, HRQoL is similar to patients found not to have diabetes. Furthermore, HRQoL scores remain stable over the year after screening. This suggests that screening for diabetes has minimal, if any, "labeling" effect with respect to HRQoL.     

Clinical and psychological course of diabetes from adolescence to young adulthood: a longitudinal cohort study

OBJECTIVE: To determine the clinical and psychological course of diabetes through adolescence and the relationship with glycemic control in young adulthood. RESEARCH DESIGN AND METHODS: A longitudinal cohort study of adolescents recruited from the register of the outpatient pediatric diabetes clinic. A total of 76 individuals (43 male patients, 33 female patients) aged 11-18 years completed baseline assessments, and 65 individuals (86%) were reinterviewed as young adults (20-28 years of age). Longitudinal assessments were made of glycemic control (HbA(1c)), weight gain (BMI), and development of complications. Adolescents completed self-report questionnaires to assess emotional and behavioral problems as well as self-esteem. As young adults, psychological state was assessed by the Revised Clinical Interview Schedule and the self-report Brief Symptom Inventory. RESULTS: Mean HbA(1c) levels peaked in late adolescence and were worse in female participants (average 11.1% at 18-19 years of age). The proportion of individuals who were overweight (BMI >25.0 kg/m(2)) increased during the 8-year period from 21 to 54% in female patients and from 2 to 28% in male patients. Serious diabetes-related events included death in one patient and cognitive impairment in two patients. Individuals in whom diabetic complications developed (25% of male patients and 38% of female patients) had significantly higher mean HbA(1c) levels than those without complications (difference 1.9%, 95% CI 1.1-2.7, P < 0.0001). Behavioral problems at baseline were related to higher mean HbA(1c) during the subsequent 8 years (beta = 0.15, SEM (beta) 0.04, P < 0.001, 95% CI 0.07-0.24). CONCLUSIONS: The outcome for this cohort was generally poor. Behavioral problems in adolescence seem to be important in influencing later glycemic control.     

A randomized,double-blind,placebo-controlled,clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus

OBJECTIVE: The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia. METHODS: Patients with type 2 diabetes mellitus (HbA(1c) >/=6.5% and /=7% to <8%) or high (>/=8% to 相似文献   

Intensified blood glucose monitoring improves glycemic control in stable,insulin-treated veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES)

OBJECTIVE: To examine the effect of intensified self-monitored blood glucose (SMBG) testing on glycemic control. RESEARCH DESIGN AND METHODS: Subjects with stable, insulin-treated type 2 diabetes performed SMBG using an electronic blood glucose meter before all meals and at bedtime for 8 weeks. Baseline data were collected on demographics, clinical characteristics, diet, and exercise. HbA(1c) was measured at baseline, at 4 weeks, and at 8 weeks. After the intensified monitoring period, subjects resumed their usual monitoring. HbA(1c) was then measured at 24, 37, and 52 weeks. Multivariate linear regression was used to determine the effect of monitoring on glycemic control. RESULTS: A total of 201 subjects completed the monitoring period. The baseline HbA(1c) (8.10 +/- 1.67%) decreased during the monitoring period by 0.30 +/- 0.68% (P < 0.001) at 4 weeks and by 0.36 +/- 0.88% (P < 0.001) at 8 weeks. Although entry HbA(1c) and compliance independently predicted the week 8 HbA(1c) (r = 0.862, P < 0.001), standardized regression analysis found that compliance with the SMBG protocol influenced the week 8 HbA(1c) more than age, sex, BMI, exercise level, carbohydrate consumption, or treatment intensity at baseline. However, SMBG benefited only subjects whose testing compliance exceeded 75% or with an entry HbA(1c) >8.0%. Decreases in HbA(1c) (-0.31 +/- 1.17%, P = 0.001) persisted in the 159 subjects followed for 52 weeks. CONCLUSIONS: Intensified blood glucose monitoring improved glycemic control in a large cohort of stable, insulin-treated veterans with type 2 diabetes. SMBG provided a strong stimulus for improved self-care resulting in clinically important and sustained reductions in HbA(1c).     

Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) present a therapeutic target, and simultaneous activation of PPAR-alpha and PPAR-gamma may provide improvements in glycemic control and dyslipidemia in patients with type 2 diabetes. OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of muraglitazar, a dual (alpha/gamma) PPAR activator, in adult patients with type 2 diabetes whose disease was inadequately controlled by diet and exercise. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 24-week monotherapy study in drug-naive, type 2 diabetes patients with inadequate glycemic control. Men and women aged 18 to 70 years with a body mass index < or =41 kg/m(2) and serum triglyceride levels < or =600 mg/dL were eligible for study participation. The study included double-blind and open-label treatment phases. Patients with glycosylated hemoglobin (HbA(1c)) levels > or =7.0% and < or =10.0% at screening were enrolled in the double-blind treatment phase. These patients received treatment with muraglitazar 2.5 mg, muraglitazar 5 mg, or placebo. Patients with HbA(1c) levels >10.0% and < or =12.0% who met all other study criteria were eligible for enrollment in a 24-week, open-label evaluation of muraglitazar 5 mg. The primary end point was the mean change from baseline in HbA(1c) levels after 24 weeks of treatment. RESULTS: A total of 340 patients (179 men, 161 women) participated in the double-blind treatment phase of the study. Patients had mean baseline HbA(1c) levels of 7.9% to 8.0%. Monotherapy with muraglitazar 2.5 and 5 mg significantly reduced HbA(1c) levels (-1.05% and -1.23%, respectively) compared with placebo (-0.32%; P < 0.001). At week 24, 58%, 72%, and 30% of the patients receiving muraglitazar 2.5 mg, muraglitazar 5 mg, and placebo, respectively, achieved the American Diabetes Association-recommended HbA(1c) goal of <7.0%. Fasting plasma glucose, free fatty acids, and fasting plasma insulin levels significantly decreased during muraglitazar treatment (P < 0.001), suggesting an increase in insulin sensitivity. Muraglitazar 2.5 and 5 mg provided improvements from baseline in triglyceride (-18% and -27%), high-density lipoprotein (HDL) cholesterol (10% and 16%), apolipoprotein B (-7% and -12%), and non-HDL cholesterol levels (-3% and -5%) (P < 0.05 vs placebo for each). In a parallel, open-label cohort of 109 drug-naive patients (56 men, 53 women; mean baseline HbA(1c) level, 10.6%), muraglitazar 5 mg decreased the overall mean HbA(1c) level from baseline by 2.62% (last observation carried forward) and by 3.49% in the 62 patients completing 24 weeks of study. Changes in lipid parameters during open-label treatment were similar to those observed during double-blind treatment. Muraglitazar was generally well tolerated. Edema-related adverse events of mild to moderate severity occurred in 8% to 11% of patients in all groups. Mean changes from baseline weight in the double-blind treatment groups were 1.1 kg for muraglitazar 2.5 mg, 2.1 kg for muraglitazar 5 mg, and -0.8 kg for placebo (P < 0.001); there was a mean 2.9-kg increase in the open-label muraglitazar 5-mg group. CONCLUSION: In this study, 24 weeks of treatment with muraglitazar 2.5 or 5 mg was an effective treatment option for these patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise.     

Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes

OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention. RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN). RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively). CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.     

Health-related quality of life and treatment satisfaction in Dutch patients with type 2 diabetes

OBJECTIVE: To estimate the health-related quality of life (HRQOL) and treatment satisfaction for patients with type 2 diabetes in the Netherlands and to examine which patient characteristics are associated with quality of life and treatment satisfaction. RESEARCH DESIGN AND METHODS: For a sample of 1,348 type 2 diabetes patients, recruited by 29 general practitioners, we collected data regarding HRQOL. This study was performed as part of a larger European study (Cost of Diabetes in Europe - Type 2 [CODE-2]). We used a generic instrument (Euroqol 5D) to measure HRQOL. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire. RESULTS: Patients without complications had an HRQOL (0.74) only slightly lower than similarly aged persons in the general population. Insulin therapy, obesity, and complications were associated with a lower HRQOL, independent of age and sex. Although higher fasting blood glucose and HbA1c levels were negatively associated with HRQOL, these factors were not significant after adjustment for other factors using multivariate analysis. Overall treatment satisfaction was very high. Younger patients, patients using insulin, and patients with higher HbA1c levels were less satisfied with the treatment than other patients. CONCLUSIONS: Obesity and the presence of complications are important determinants of HRQOL in patients with type 2 diabetes.     

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

OBJECTIVE: The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control (glycosylated hemoglobin [HbA(1c)] > or =7% and < or =10%) while receiving a stable dose of pioglitazone. METHODS: This was a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients aged > or =18 years (ClinicalTrials. gov NCT00086502). At screening, all patients began a diet/exercise program that continued throughout the study period. Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period. Patients with an HbA(1c) > or =7% and < or =10% at the end of this period entered a 2-week, single-blind, placebo run-in period (total duration of run-in period, up to 21 weeks). Patients who had been receiving pioglitazone monotherapy (30 or 45 mg/d) and had an HbA(1c) > or =7% and < or =10% entered the 2-week, single-blind, placebo run-in period directly. Thus, at the time of randomization, all patients were receiving ongoing pioglitazone (30 or 45 mg/d). Patients were randomized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) at week 24. Secondary efficacy end points included the change from baseline in fasting plasma glucose (FPG), insulin, and proinsulin; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes; the proinsulin/ insulin ratio; the Quantitative Insulin Sensitivity Check Index; the percent changes from baseline in selected lipid parameters; the proportion of patients meeting the American Diabetes Association HbA(1c), goal of <7.0%; the proportion of patients requiring metformin rescue therapy; and the time to the initiation of rescue therapy. RESULTS: One hundred seventy-five patients were randomized to receive sitagliptin, and 178 were randomized to receive placebo. The mean (SD) baseline HbAlc value was 8.1% (0.8) in the sitagliptin group and 8.0% (0.8) in the placebo group. After 24 weeks, sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c) (between-treatment difference in least squares [LS] mean change from baseline. -0.70 %; 95 % CI, -0.85 to -0.54; P < 0.001) and FPG (-17.7 mg/dL; 95% CI, -24.3 to -11.0; P < 0.001). Mean HbA(1c) values at end point were 7.2% (0.9) and 7.8% (1.1) in the respective treatment groups, and the proportions of patients reaching a target HbA(1c) of <7.0% were 45.4% and 23.0% (P < 0.001). Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo (both, P < 0.01). Sitagliptin was generally well tolerated, with no increased risk of hypoglycemia compared with placebo (2 vs 0 patients, respectively).     

Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes

OBJECTIVE: To evaluate the safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: All 95 patients who began insulin pump therapy at Johns Hopkins Hospital between January 1990 and December 2000 were included in the study. The mean age was 12.0 years (range 4-18), and 29% of the patients were <10 years old. Data were obtained by chart review beginning 6-12 months before pump start. The median duration of follow-up was 28 months. RESULTS: There was a small but significant decrease in HbA(1c) at 3-6 months after pump start (7.7 vs. 7.5%; P = 0.03). HbA(1c) levels then gradually increased and remained elevated after 1 year of follow-up; however, this association was confounded by age and diabetes duration, both of which were associated with higher HbA(1c) levels. After adjusting for duration and age, mean HbA(1c) after pump start was significantly lower than before pump start (7.7 vs. 8.1%; P < 0.001). The number of medical complications (diabetic ketoacidosis, emergency department visits) was similar before and after pump start. There were fewer hypoglycemic events after pump start (12 vs. 17, rate ratio 0.46, 95% CI 0.21-1.01). CONCLUSIONS: This study suggests that pump therapy is safe and effective in selected children and adolescents with type 1 diabetes.     

Optimal blood glucose control during 18 years preserves peripheral nerve function in patients with 30 years' duration of type 1 diabetes

OBJECTIVE: To assess the association between 18 years of mean HbA(1c) and nerve conduction parameters of the lower limb in patients with type 1 diabetes of 30 years' duration. RESEARCH DESIGN AND METHODS: HbA(1c) has been examined prospectively since 1982 in a group of 39 patients with type 1 diabetes. Mean age at baseline was 25 years (range 18-40) with 12 years' disease duration. The mean age at diagnosis of diabetes was 12.5 years. Nerve function of lower limbs was assessed at baseline, after 8 years, and after 18 years. RESULTS: A total of 23 men and 16 women were studied. Mean age was 43 years. Mean HbA(1c) was 8.2% (range 6.6-11.3) during 18-year follow-up. Nerve conduction velocity (NCV) and nerve action potential amplitude (NAPA) at the last examination were significantly associated with mean HbA(1c) (P < 0. 05). From 1982 to 1999, there was a significant reduction in nerve function in patients with mean HbA(1c) >or=8.4% (highest tertile). For example, the mean NCV in the tibial nerve was reduced from 47 to 31 m/s (P < 0.01). The number of nerves with NCV (P < 0.01) and NAPA (P = 0.01) reduced to below the reference level in each patient was also significantly associated to mean HbA(1c). No significant associations were found between nerve function parameters, sex, disease duration, blood pressure, serum cholesterol, microalbuminuria, or smoking. CONCLUSIONS: The present study shows that mean HbA(1c) is a strong predictor of nerve function. Mean HbA(1c) <8.4% over 18 years was associated with near-normal nerve function.     

The Relationship of Plasma Glucose and HbA1c Levels among Emergency Department Patients with No Prior History of Diabetes Mellitus

Objectives: Patients without a history of diabetes mellitus may be incidentally found to be hyperglycemic in the emergency department (ED). If the hyperglycemia is due to undiagnosed diabetes, then an opportunity for detection exists. Hemoglobin A1c (HbA1c) provides a weighted average of blood glucose levels over the past several months; high HbA1c levels could indicate diabetes. The objective of this study was to determine whether hyperglycemia in ED patients without a history of diabetes was associated with higher HbA1c levels.
Methods: This was a prospective nonconsecutive case series of adults aged 18 years or older presenting to the ED with acute illness for whom a plasma glucose sample was drawn for clinical management. A history of diabetes/hyperglycemia or current symptoms of diabetes excluded patients. HbA1c levels were analyzed for a glucose cutoff of 110 mg/dL; the data were further analyzed using additional glucose cutoffs. Based on the Third National Health and Nutrition Examination Survey outpatient screening data, an HbA1c level ≥6.2% was considered elevated (sensitivity of 63% and specificity of 97% for identifying diabetes).
Results: There were 541 patients enrolled; the glucose level correlated with the HbA1c level ( r = 0.60, p < 0.001). Among the 331 patients with a glucose level ≥110 mg/dL, 22.4% had an elevated HbA1c level; among the 210 patients with a glucose level < 110 mg/dL, 7.6% had an elevated HbA1c level. There were few patients ( n = 13) with a glucose level ≥200 mg/dL, but most (85%) had an elevated HbA1c level. Among the 140 patients with a mildly elevated glucose level (110–125 mg/dL), 16.4% had an elevated HbA1c level.
Conclusions: Elevated HbA1c levels are found in ED patients with elevated random plasma glucose values. ED patients with hyperglycemia may warrant referral for diabetes testing.     

Eighteen years of fair glycemic control preserves cardiac autonomic function in type 1 diabetes

OBJECTIVE: To study the association between 18 years of mean HbA(1c) and cardiac autonomic function in type 1 diabetic patients having used intensive insulin treatment. RESEARCH DESIGN AND METHODS: A total of 39 patients with type 1 diabetes were followed during 18 years, and HbA(1c) was measured yearly. At 18 years follow-up heart rate variability (HRV) measurements were used to assess cardiac autonomic function. Standard cardiac autonomic tests during normal breathing, deep breathing, the Valsalva maneuver, and the tilt test were performed. Maximal heart rate increase during exercise electrocardiogram and minimal heart rate during sleep were also used to describe cardiac autonomic function. RESULTS: We present the results for patients with mean HbA(1c) <8.4% (two lowest HbA(1c) tertiles) compared with those with HbA(1c) > or = 8.4% (highest HbA(1c) tertile). All of the cardiac autonomic tests were significantly different in the high- and the low-HbA(1c) groups, and the most favorable scores for all tests were seen in the low-HbA(1c) group. In the low-HbA(1c) group, the HRV was 40% during deep breathing, and in the high-HbA(1c) group, the HRV was 19.9% (P = 0.005). Minimal heart rate at night was significantly lower in the low-HbA(1c) groups than in the high-HbA(1c) group (P = 0.039). With maximal exercise, the increase in heart rate was significantly higher in the low-HbA(1c) group compared with the high-HbA(1c) group (P = 0.001). CONCLUSIONS: Mean HbA(1c) during 18 years was associated with cardiac autonomic function. Cardiac autonomic function was preserved with HbA(1c) <8.4%, whereas cardiac autonomic dysfunction was impaired in the group with HbA(1c) > or = 8.4%.     

Establishment of blood glucose monitoring system using the internet

OBJECTIVE: The Internet is used worldwide as a communication tool. To improve the quality of diabetes control, we investigated the effectiveness of an Internet-based blood glucose monitoring system (IBGMS) on controlling the changes in HbA(1c) levels. RESEARCH DESIGN AND METHODS: We conducted a randomized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary's Hospital for 3 months. The study subjects were treated with IBGMS for 12 weeks, and the control group received the usual outpatient management over the same period. HbA(1c) and other laboratory tests were performed twice, once at the beginning of the study and again at the end of the study. RESULTS: The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age, sex, diabetes duration, BMI, blood pressure, HbA(1c), and other laboratory data. On follow-up examination 12 weeks later, HbA(1c) levels were significantly decreased from 7.59 to 6.94% within the intervention group (P < 0.001). At the end of the study, HbA(1c) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c) (6.94 vs. 7.62%; P < 0.001, respectively). Among patients with baseline HbA(1c) <7.0%, the patients in the intervention group had lower HbA(1c) than those in the control group (6.38 vs. 6.99%; P < 0.05). Among the patients with a baseline HbA(1c) > or = 7.0%, the difference between the two groups appeared more obvious: HbA(1c) levels at the end of the study were 8.12%. CONCLUSIONS: This new IBGMS resulted in a significant reduction of HbA(1c) during the study period. We propose that this IBGMS be used as a method for improving diabetes control.     

Diabetes management in a health maintenance organization. Efficacy of care management using cluster visits

OBJECTIVE: To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS: This study involved a randomized controlled trial among patients of Kaiser Permanente's Pleasanton, CA, center who were aged 16-75 years and had either poor glycemic control (HbA1c > 8.5%) or no HbA1c test performed during the previous year. Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator, a psychologist, a nutritionist, and a pharmacist in cluster visit settings of 10-18 patients/month for 6 months. Outcomes included change (from baseline) in HbA1c levels; self-reported changes in self-care practices, self-efficacy, and satisfaction; and utilization of inpatient and outpatient health care. RESULTS: After the intervention, HbA1c levels declined by 1.3% in the intervention subjects versus 0.2% in the control subjects (P < 0.0001). Several self-care practices and several measures of self-efficacy improved significantly in the intervention group. Satisfaction with the program was high. Both hospital (P = 0.04) and outpatient (P < 0.01) utilization were significantly lower for intervention subjects after the program. CONCLUSIONS: A 6-month cluster visit group model of care for adults with diabetes improved glycemic control, self-efficacy, and patient satisfaction and resulted in a reduction in health care utilization after the program.     

Dietary fats do not contribute to hyperlipidemia in children and adolescents with type 1 diabetes

OBJECTIVE: To determine the relative influence of diet, metabolic control, and familial factors on lipids in children with type 1 diabetes and control subjects. RESEARCH DESIGN AND METHODS: We assessed fasting serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein (apo)-A1, and apoB in 79 children and adolescents with type 1 diabetes and 61 age- and sex-matched control subjects, together with dietary intakes using a quantitative food frequency questionnaire. RESULTS: Total cholesterol, LDL cholesterol, apoB, HDL cholesterol, and apoA1 were significantly higher in children with diabetes. Children with diabetes had higher percentage energy intake from complex carbohydrates (P = 0.001) and fiber intake (P = 0.02), and they had lower intake of refined sugar (P < 0.001) and percentage energy from saturated fat (P = 0.045) than control subjects. Total cholesterol (beta = 0.43, P < 0.001), LDL cholesterol (beta = 0.4, P < 0.001), and apoB (beta = 0.32, P = 0.006) correlated independently with HbA(1c) but not dietary intake. HDL cholesterol (beta = 0.24, P = 0.05) and apoA1 (beta = 0.32, P = 0.004) correlated independently with HbA(1c), and HDL cholesterol (beta = -0.34, P = 0.009) correlated with percentage energy intake from complex carbohydrates. Triglycerides correlated independently with percentage energy intake from complex carbohydrates (beta = 0.33, P = 0.01) and insulin dose (beta = 0.26, P = 0.04). Subjects with diabetes and elevated LDL (>3.35 mmol/l, >130 mg/dl), for whom dietary therapy would be recommended, had significantly higher HbA(1c) (P = 0.007), but they had higher intake of complex carbohydrates than subjects with LDL cholesterol <3.35 mmol/l. CONCLUSIONS: Lipid abnormalities remain common in children and adolescents with type 1 diabetes who adhere to current dietary recommendations, and they relate to metabolic control but not dietary intake.