Lynda K. Fisher

Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: The TODAY clinical trial

OBJECTIVE Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. RESEARCH DESIGN AND METHODS A cohort of 699 adolescents, 10–17 years of age, <2 years duration of type 2 diabetes, BMI ≥85%, HbA1c ≤8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg. RESULTS In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria. CONCLUSIONS Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.

Insulin pump therapy in Type 1 pediatric patients: now and into the year 2000

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia.

Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial

BACKGROUND Type 1 diabetes results from T-cell-mediated destruction of β cells. Findings from preclinical studies and pilot clinical trials suggest that antithymocyte globulin (ATG) might be effective for reducing this autoimmune response. We assessed the safety and efficacy of rabbit ATG in preserving islet function in participants with recent-onset type 1 diabetes, and report here our 12-month results. METHODS For this phase 2, randomised, placebo-controlled, clinical trial, we enrolled patients with recent-onset type 1 diabetes, aged 12-35 years, and with a peak C-peptide of 0.4 nM or greater on mixed meal tolerance test from 11 sites in the USA. We used a computer generated randomisation sequence to randomly assign patients (2:1, with permuted-blocks of size three or six and stratified by study site) to receive either 6.5 mg/kg ATG or placebo over a course of four days. All participants were masked and initially managed by an unmasked drug management team, which managed all aspects of the study until month 3. Thereafter, to maintain masking for diabetes management throughout the remainder of the study, participants received diabetes management from an independent, masked study physician and nurse educator. The primary endpoint was the baseline-adjusted change in 2-h area under the curve C-peptide response to mixed meal tolerance test from baseline to 12 months. Analyses were by intention to treat. This is a planned interim analysis of an on-going trial that will run for 24 months of follow-up. This study is registered with ClinicalTrials.gov, number NCT00515099. FINDINGS Between Sept 10, 2007, and June 1, 2011, we screened 154 individuals, randomly allocating 38 to ATG and 20 to placebo. We recorded no between-group difference in the primary endpoint: participants in the ATG group had a mean change in C-peptide area under the curve of -0.195 pmol/mL (95% CI -0.292 to -0.098) and those in the placebo group had a mean change of -0.239 pmol/mL (-0.361 to -0.118) in the placebo group (p=0.591). All except one participant in the ATG group had both cytokine release syndrome and serum sickness, which was associated with a transient rise in interleukin-6 and acute-phase proteins. Acute T cell depletion occurred in the ATG group, with slow reconstitution over 12 months. However, effector memory T cells were not depleted, and the ratio of regulatory to effector memory T cells declined in the first 6 months and stabilised thereafter. ATG-treated patients had 159 grade 3-4 adverse events, many associated with T-cell depletion, compared with 13 in the placebo group, but we detected no between-group difference in incidence of infectious diseases. INTERPRETATION Our findings suggest that a brief course of ATG does not result in preservation of β-cell function 12 months later in patients with new-onset type 1 diabetes. Generalised T-cell depletion in the absence of specific depletion of effector memory T cells and preservation of regulatory T cells seems to be an ineffective treatment for type 1 diabetes.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009

To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus.

Diabetes management in correctional institutions.

A t any given time, over 2 million people are incarcerated in prisons and jails in the U.S (1). It is estimated that nearly 80,000 of these inmates have diabetes, a prevalence of 4.8% (2). In addition, many more people pass through the corrections system in a given year. In 1998 alone, over 11 million people were released from prison to the community (1). The current estimated prevalence of diabetes in correctional institutions is somewhat lower than the overall U.S. prevalence of diabetes, perhaps because the incarcerated population is younger than the general population. The prevalence of diabetes and its related comorbidities and complications, however, will continue to increase in the prison population as current sentencing guidelines continue to increase the number of aging prisoners and the incidence of diabetes in young people continues to increase. People with diabetes in correctional facilities should receive care that meets national standards. Correctional institutions have unique circumstances that need to be considered so that all standards of care may be achieved (3). Correctional institutions should have written policies and procedures for the management of diabetes and for training of medical and correctional staff in diabetes care practices. These policies must take into consideration issues such as security needs, transfer from one facility to another, and access to medical personnel and equipment, so that all appropriate levels of care are provided. Ideally, these policies should encourage or at least allow patients to self-manage their diabetes. Ultimately, diabetes management is dependent upon having access to needed medical personnel and equipment. Ongoing diabetes therapy is important in order to reduce the risk of later complications, including cardiovascular events, visual loss, renal failure, and amputation. Early identification and intervention for people with diabetes is also likely to reduce short-term risks for acute complications requiring transfer out of the facility, thus improving security. This document provides a general set of guidelines for diabetes care in correctional institutions. It is not designed to be a diabetes management manual. More detailed information on the management of diabetes and related disorders can be found in the American Diabetes Association (ADA)Clinical Practice Recommendations, published each year in January as the first supplement to Diabetes Care, as well as the “Standards ofMedical Care in Diabetes” (4) contained therein. This discussion will focus on those areas where the care of people with diabetes in correctional facilities may differ, and specific recommendations are made at the end of each section.

The selection of children and adolescents for treatment with continuous subcutaneous insulin infusion (CSII)

Abstract:  Continuous subcutaneous insulin infusion (CSII) was first introduced as a mode of treatment for persons with type 1 diabetes mellitus (T1DM) in the late 1970s. Since that time, there have been many reports and reviews of this modality of treatment in adults and adolescents with diabetes and several reports of the use of this technology in the treatment of children with T1DM. Conflicting data have accumulated on the consistency of improvement in hemoglobin A1c (HbA1c) and in the frequency of complications, most significantly that of hypoglycemia. Some studies report the findings of controlled randomized studies, but many of these studies were conducted on small numbers of highly selected patients. Some studies are prospective but not randomized, where subjects pre‐CSII serve as their own controls. Yet other studies are retrospective reviews of children and adolescents who have been treated with CSII. This paper reviews what has been learned about patient selection and outcomes of CSII treatment, with the goal of outlining steps in the selection and preparation of patients for CSII that will facilitate optimum outcome.

Short stature and metabolic abnormalities in two sisters with a 7.6-kb GH1 gene deletion

UNLABELLED Growth hormone 1 (GH1) gene deletions occur in approximately 10-15% of patients with severe isolated, GH deficiency (GHD). The standard treatment for GHD is GH replacement. Individuals with GH gene defects, however, may form GH antibodies that interfere with the efficacy of exogenous recombinant GH (rhGH) therapy. OBJECTIVE We describe the growth measures and metabolic studies of two Hispanic sisters with the same 7.6-kb GH1 gene deletion who presented with short stature and increased body fat, and who developed neutralizing GH antibodies secondary to rhGH exposure. DESIGN The younger sister has now been treated with recombinant human insulin-like growth factor-I (rhIGF-I) for 4 years, and is continuing treatment. The older sister was not given rhIGF-I based on her normal height velocity and age. After the first 4 years of rhIGF-I treatment of the younger sister, we summarized the longitudinal anthropometric measures and serial laboratory studies, including GH surrogates, fasting lipid studies, oral glucose tolerance tests, and HbA1c, of both sisters. Body composition was quantified using DEXA analysis. RESULTS The older sister achieved an adult stature at the low end of her mid-parental target height range, having been treated only with rhGH for ~2.5 years (between 11 months and 3.5 years of age). Treatment of the younger sister with rhIGF-I for 4 years has led to persistent improvement in height velocity, but was associated with adverse short-term effects on all lipids. Her BMI increased modestly (+4.1 kg/m(2)) during rhIGF-I treatment, though her change in percent body fat was negligible by DEXA (Δ -0.7%). CONCLUSIONS In individuals with a GH gene deletion, rhIGF-I promotes increased height velocity, but may be associated with adverse effects on lipids and BMI. It is clear that the long-term effects of rhIGF-I on lipid metabolism and body composition require further monitoring and assessment with continued treatment.

Targets and teamwork: Understanding differences in pediatric diabetes centers treatment outcomes

The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009: Center differences persist in young children

To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers

To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus.