Rubina A. Heptulla

Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome.

OBJECTIVE We evaluated the hypothesis that metformin would improve signs and symptoms of polycystic ovary syndrome (PCOS) in adolescents as compared to oral contraceptive pills (OCP) and have a favorable effect on obesity. STUDY DESIGN Thirty-five obese, post-menarchal, non-sexually active adolescents aged 12-21 years with PCOS and hyperinsulinism were randomly assigned to receive either OCP or metformin for 6 months. RESULTS There was a significant decrease in BMI in the two groups over time, from 40.1 to 38.6 in the OCP group, and 37.3 to 36.3 in the metformin group, p = 0.0026, but no significant difference in the degree of change between the two groups. Both groups had decreased free testosterone (OCP: 1.8 pg/ml to 0.96 pg/ml; metformin: 2.1 pg/ml to 1.6 pg/ml), p < 0.0001, and improvements in insulin resistance as evidenced by increased glucose/insulin (G/I) ratio (p < 0.005) and increased QUICK1 scores (p < 0.0005). No significant differences in response to treatment were found between the metformin and OCP groups in outcome variables. CONCLUSION Adolescents with PCOS treated with metformin or OCP experienced similar beneficial outcomes including reduction in androgen levels, weight loss, and increased insulin sensitivity. The choice of a treatment agent for long-term use will depend on safety profiles, therapeutic goals and patient adherence.

The Role of Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes

OBJECTIVE Exenatide improves postprandial glycemic excursions in type 2 diabetes. Exenatide could benefit type 1 diabetes as well. We aimed to determine an effective and safe glucose-lowering adjuvant exenatide dose in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Eight subjects completed a three-part double-blinded randomized controlled study of premeal exenatide. Two doses of exenatide (1.25 and 2.5 μg) were compared with insulin monotherapy. Prandial insulin dose was reduced by 20%. Gastric emptying and hormones were analyzed for 300 min postmeal. RESULTS Treatment with both doses of exenatide versus insulin monotherapy significantly reduced glucose excursions over 300 min (P < 0.0001). Exenatide administration failed to suppress glucagon but delayed gastric emptying (P < 0.004). CONCLUSIONS Adjunctive exenatide therapy reduces postprandial hyperglycemia in adolescents with type 1 diabetes. This reduction in glucose excursion occurs despite reduction in insulin dose. We suggest that exenatide has therapeutic potential as adjunctive therapy in type 1 diabetes.

Glycemic Control in Pediatric Type 1 Diabetes: Role of Caregiver Literacy

OBJECTIVE: Poorly controlled diabetes may occur because caregivers of children with type 1 diabetes fail to comprehend provided diabetes education. We hypothesized that poorly controlled diabetes is associated with lower literacy/numerical skills of caregivers of children with type 1 diabetes. METHODS: Primary caregivers were evaluated by using Newest Vital Sign (NVS) and a sociodemographic questionnaire. The NVS identifies individuals who are at risk for low health literacy by measuring general literacy/numeracy skills and yields an overall estimate of health literacy. The NVS scores are interpreted to suggest inadequate, limited, or adequate literacy. RESULTS: Two hundred caregivers of children who had type 1 diabetes with mean hemoglobin A1c (HbA1c) of 8.8 ± 1.9%, age of 11.8 ± 3.7 years, duration of disease of 4.8 ± 3.3 years, and BMI of 20.8 ± 4.4 kg/m2 participated. HbA1c in those of inadequate literacy (10.4 ± 2.2%) was significantly higher than in those of adequate literacy (8.6 ± 1.7%; P < .001). HbA1c in those whose caregivers had limited literacy (9.5 ± 2.2%) did not differ significantly from the other 2 groups. On adjusting for independent covariates, we found that children whose caregivers had at least 50% correct math answers had better glycemic control (8.5 ± 1.7%) than those who failed (9.8 ± 2.1%; P < .0005). CONCLUSIONS: Literacy and numerical skills of caregivers significantly influence glycemic control of their children with type 1 diabetes. Assessing literacy/numeracy skills of caregivers and addressing these deficiencies may be crucial in optimizing glycemic control.

A Randomized, Controlled Trial Comparing Twice-a- Day Insulin Glargine Mixed With Rapid-Acting Insulin Analogs Versus Standard Neutral Protamine Hagedorn (NPH) Therapy in Newly Diagnosed Type 1 Diabetes

OBJECTIVE. Insulin glargine is difficult to use for children due to the number of injections required because it is claimed to be immiscible with rapid-acting insulin analogs. For this study, we hypothesized that treating new-onset type 1 diabetes with twice-daily insulin glargine plus a rapid-acting insulin analog mixed in the same syringe would result in better glycosylated hemoglobin than twice-daily neutral protamine Hagedorn with a rapid-acting insulin analog (standard treatment). METHODS. Forty-two patients with new-onset type 1 diabetes were started on standard treatment. Three months after diagnosis, if patients were found compliant and had a glycosylated hemoglobin level of ≤9%, then they were randomly assigned either to receive insulin glargine twice daily mixed with a rapid-acting insulin analog or to continue on standard treatment for 3 more months. Additional lunchtime rapid-acting insulin analog injections were given for the insulin glargine group as necessary. RESULTS. Nineteen patients in the insulin glargine group and 17 in the neutral protamine Hagedorn group completed the study. The glycosylated hemoglobin level at baseline was 6.8% ± 1% vs 6.9% ± 1% and at poststudy was 6.7% ± 1.3% vs 7.6% ± 1% in the insulin glargine versus neutral protamine Hagedorn group, respectively. Two patients in the insulin glargine group required lunch rapid-acting insulin analog in the last month of the study. Although both groups were encouraged to contact the principal investigator with all queries, more in the insulin glargine arm opted to do so. CONCLUSIONS. Glycemic control with insulin glargine mixed with a rapid-acting insulin analog given twice daily seems significantly more effective than the standard therapy in newly diagnosed type 1 diabetes. Furthermore, it decreases pain and burden of injections for children with diabetes by allowing patients to mix glargine with rapid-acting insulin analog.

Effects of Mixing Glargine and Short-Acting Insulin Analogs on Glucose Control

Intensive insulin management improves glycemic control and lowers the risks of long-term microvascular complications (1). Several new insulin analogs (2) are in use to improve glycemic control in type 1 diabetes. Glargine in particular is a “basal insulin” (3) and found to be relatively peakless. Glargine is thought to provide glucose profiles similar to insulin pumps (4). Although some clinical studies suggest that glargine lasts 24 h in children with diabetes (5), to date there have been no formal pharmacokinetic and pharmacodynamic data to make that claim in the pediatric population. In fact, clinical observations in pediatric type 1 diabetes suggest that glargine action may be <24 h. This would entail twice-daily glargine dosing and short-acting insulin analogs (SAIs), such as lispro and aspart, given separately three to four times per day, resulting in improved glycemic control but compromising compliance and increasing complexity of management (6). In this study, we tested the hypothesis that mixing glargine with SAIs and dividing the dose of glargine into twice- versus once-daily dosing would not adversely affect glycemic control as assessed by a continuous glucose monitoring system (CGMS). The protocol was approved by the institutional review board of the Baylor College of Medicine, and consent was obtained before each study. Subjects were recruited from Texas Children’s Hospital Diabetes Care Center, Houston, Texas. Subjects had type 1 diabetes for at least 1 year with no other chronic illness and were on …

Continuous glucose monitoring in children with type 1 diabetes: before and after insulin pump therapy.

Abstract:  Objective:   The aim of continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM) is to mimic as closely as possible the normal physiologic pattern seen in individuals without diabetes. This study was undertaken to determine the specific areas of improved glycemic control in subjects after initiation of insulin pump therapy and times where further improvement is needed.

The role of prandial pramlintide in the treatment of adolescents with type 1 diabetes.

Pramlintide, a synthetic analog of amylin, improves postprandial hyperglycemia. We compared subcutaneous (s.c.) pramlintide injection with square wave pramlintide infusion in adolescents with type 1 diabetes (T1DM). Eight subjects with T1DM underwent two randomized studies. Subcutaneous pramlintide (dose = 5 μg/unit of insulin) bolus, was given one time and another time, the same dose was given as a 120-min s.c. infusion. Insulin dose was constant between studies. Gastric emptying was assessed with oral acetaminophen and [l-13C]glucose in meal. Plasma glucagon, pramlintide, and insulin concentrations were measured. Insulin concentrations (p < 0.99) between pramlintide injection versus infusion were similar; however, glucose concentrations were different (p < 0.0001), with the absence of hypoglycemia during pramlintide infusion [AUC (0–120 min) −0.07 ± 0.2 versus 1.05 ± 0.24 mg * h/dL (p < 0.0088)]. Insulin-only administration resulted in postprandial hyperglycemia and late postprandial hypoglycemia (p < 0.0001). Two subjects experienced hypoglycemia with pramlintide injection. Pramlintide bolus caused pronounced glucagon suppression (p < 0.0003) and delayed gastric emptying as ([13CO2] p < 0.0003 and acetaminophen p < 0.01) compared with infusion. We conclude that pramlintide bolus may result in an increase in risk of immediate postprandial hypoglycemia. Further modifications in pramlintide delivery are indicated before it can be safely used in children.

Cardiac response to progressive cycle exercise in moderately obese adolescent females

PURPOSE To assess cardiac responses to exercise and cardiac functional capacity in moderately obese adolescent females. METHODS Thirteen healthy females (mean age 13.6 +/- 1.5 years) with a body mass index from 30 to 43 kg per m(2) underwent maximal cycle testing. Cardiac responses were measured by Doppler echocardiogram, and gas exchange variables were determined with open circuit spirometry. Data were analyzed by independent Students t-tests. RESULTS Peak oxygen uptake relative to height(3.0) was significantly greater in the obese (570 +/- 90 ml m(-3)) compared to the nonobese controls (485 +/- 60 ml m(-3)). This difference was explained by a higher peak cardiac output (4.50 +/- 1.06 L m(-3) vs. 3.81 +/- 58 L m(-3)) and stroke volume (24 +/- 5 ml m(-3) vs. 19 +/- 3 ml m(-3)) in the obese. Maximal cardiac index was similar in the two groups. There was no evidence of myocardial dysfunction during exercise in either group. CONCLUSIONS Low aerobic fitness in obese adolescents as indicated by depressed peak VO(2) per kg body mass and limited endurance performance does not reflect decreased cardiac functional capacity.

Targeting blood glucose management in school improves glycemic control in children with poorly controlled type 1 diabetes mellitus.

We hypothesized that school nurse supervision of glucose and insulin-dose adjustment significantly improves the hemoglobinA(1c) (HbA(1c)) level in pediatric patients with poorly controlled type 1 diabetes mellitus (HbA(1c) > or = 9%). A total of 36 subjects were enrolled and 18 subjects were randomized to receive the 3-month intervention. Their average HbA(1c) was lowered by 1.6%, suggesting that this intervention helps this difficult group of patients.

Predictors of direct costs of diabetes care in pediatric patients with type 1 diabetes

Ying AK, Lairson DR, Giardino AP, Bondy ML, Zaheer I, Haymond MW, Heptulla RA. Predictors of direct costs of diabetes care in pediatric patients with type 1 diabetes.