Orit Pinhas-Hamiel

Acute and chronic complications of type 2 diabetes mellitus in children and adolescents

With the increase in prevalence of type 2 diabetes mellitus in adolescents, a rise in incidence of secondary comorbidities--including hypertension, hyperlipidaemia, nephropathy, and retinopathy--is anticipated. Furthermore, findings of studies in young adults have suggested that the development and progression of clinical complications might be especially rapid when the onset of type 2 diabetes is early, raising the possibility of a serious public-health challenge in the next few decades. To date, reports of the epidemiology and natural history of secondary complications specifically in adolescents with type 2 diabetes have been scarce. Yet, we must begin to understand the extent of the coming challenge. To this end, we have reviewed reports on acute and long-term comorbidities associated with type 2 diabetes in young people and have looked at mounting evidence that this group could be at increased risk for development of early complications.

Diabetic Ketoacidosis Among Obese African-American Adolescents With NIDDM

OBJECTIVE To determine whether ketosis at the time of presentation occurs among African-American adolescents with NIDDM. RESEARCH DESIGN AND METHODS We reviewed the charts of all islet cell antibody (ICA) negative patients diagnosed with NIDDM at Childrens Hospital Medical Center (CHMC) between 1982 and 1995. RESULTS Between 1982 and 1985, 70 adolescents were diagnosed with NIDDM. Of these, ICA determinations were available and negative on 42 subjects (28 African-American, 12 white). Twelve of 28 (42%) African-American patients presented with ketonuria, and seven of 28 (25%) presented with DKA. In comparison, none of the 12 white adolescents with NIDDM had ketonuria at presentation or during their subsequent course. Mean follow-up time for patients with ketosis at presentation was 24 months. There was no difference between the age, BMI, or sex distribution of patients with and without ketosis. Previously diagnosed hypertension was present in 42% of patients presenting with ketosis, compared with 17% of the general NIDDM population at CHMC. CONCLUSIONS We conclude that ketosis may occur among African-American adolescents with NIDDM, as has been previously reported among African-American adults with NIDDM. Therefore, ketosis in obese young African-American patients with new-onset diabetes does not necessarily imply the presence of IDDM and insulin dependence.

Clinical presentation and treatment of type 2 diabetes in children

Abstract:  Type 2 diabetes mellitus (T2DM) has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. This increase has also affected the young such that over the past decade, the increase in the number of children and youth with T2DM has been labeled an ‘epidemic’. Before the 1990s, it was rare for most pediatric centers to have significant numbers of patients with T2DM. However, by 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas and by 1999, depending on geographic location, the range of percentage of new cases because of T2DM was 8–45% and disproportionately represented among minority populations. Although the diagnosis was initially regarded with skepticism, T2DM is now a serious diagnostic consideration in all young people who present with signs and symptoms of diabetes in the USA.

Lipid and Insulin Levels in Obese Children : Changes with Age and Puberty

Objective: The goal was to describe the lipid profile and insulin changes seen in obese children and adolescents at different stages of puberty.

Juvenile multiple sclerosis: Clinical features and prognostic characteristics

In a retrospective study we analyzed clinical features and their prognostic significance in 72 patients with onset of multiple sclerosis by the age of 21 years. In juvenile multiple sclerosis disease progression does not depend on age of onset, severity of neurologic involvement, or polysymptomatic or monosymptomatic involvement at presentation.

Headaches in overweight children and adolescents referred to a tertiary-care center in Israel.

Objective: To assess the association between obesity and primary headaches in children and adolescents.

Treatment of Congenital Hyperinsulinism with Lanreotide Acetate (Somatuline Autogel)

CONTEXT Congenital hyperinsulinism (CH) may be treated conservatively in many children with octreotide given by multiple sc injections or via an insulin pump. OBJECTIVE We describe two children treated with a once-monthly injection of a long-acting somatostatin analog. PATIENTS AND METHODS Both patients presented with hypoglycemia 30 min after birth and were subsequently diagnosed with CH. Patients were initially treated with diazoxide, hydrochlorothiazide, frequent feedings, and octreotide via an insulin pump. With this therapy, they were normoglycemic with a good growth rate, normal weight gain, and excellent neurodevelopment. Treatment with the long-acting somatostatin analog lanreotide acetate (Somatuline Autogel), administered by deep sc injection of 30 mg once a month, was started at the ages of 4½ and 4 yr, respectively. Octreotide infusion was gradually weaned over 1 month. Continuous glucose monitoring after discontinuation of pump therapy showed normoglycemia. The first patient has now been treated with the lanreotide acetate for over 5 yr, and the second for 3 yr. Treatment is well-tolerated, and both the patients and their parents are satisfied with the transition from pump therapy to once-a-month injection and prefer it to pump therapy. CONCLUSION Lanreotide acetate may be a safe and effective alternative to octreotide pump therapy in patients with CH, offering an improved quality of life. Longer follow-up of a larger patient group is needed.

Immunogenetics of HLA class II in Israeli Ashkenazi Jewish, Israeli non-Ashkenazi Jewish, and in Israeli Arab IDDM patients

The distribution of HLA class II alleles and genotypes in IDDM patients was examined in the three main Israeli ethnic groups: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. Molecular sequence specific oligonucleotide probe analysis was performed for DRB1, DQA1, and DQB1 genes. The DRB1*03011, DQA1*05 DQB1*02/DRB1*0402, DQA1*03, DQB1*0302 genotype was found to be the main susceptibility genotype in all three groups, with differences in the degree of association. In addition to DRB1*0402 (more frequent among Ashkenazi Jews), DRB1*0405, another subtype of DRB1*04, was found to be more prevalent among non-Ashkenazi Jews and Arabs. Many alleles were found to be negatively associated with insulin dependent diabetes mellitus (IDDM). This could be a result of the high frequency of susceptible alleles, or of linkage disequilibrium to a primary negatively associated allele. The strongest negative association was observed for DQB1*0301 in all three ethnic groups. The alleles DRB1*1401, DRB1*1501, DQB1*05031, DQB1*0602, and DQB1*0609 were not detected in any of the 202 IDDM patients, and are probably either strongly protective or in linkage with such alleles. Despite the differences found between the three ethnic groups, an overall analysis shows that the DRB1*04 alleles that account for susceptibility to IDDM in the Israeli population (DRB1*0402 and *0405) are the same as those responsible for susceptibility to IDDM in a number of other Mediterranean populations. In contrast, the susceptible allele in most Caucasian populations is DRB1*0401. It is noteworthy that the susceptible alleles DRB1*0402/05 for Mediterranean and DRB1*0401 for Caucasian populations are also frequent in the respective healthy populations. These findings support the results obtained in other studies, which point to a genetic relationship between the Israeli and Mediterranean populations.

Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism

BACKGROUND Congenital hyperinsulinism (CH) is treated surgically in many centers (near-total and partial pancreatectomy for diffuse and focal disease respectively). Most patients treated with near-total pancreatectomy developed diabetes during childhood/puberty. CH patients are at increased risk of neurodevelopmental disorders, some being severe, which are reported to occur in 14-44% of patients from highly heterogenous cohorts. Over the last few decades, we have treated children with CH conservatively without surgery. The aim of this study was to assess the neurodevelopmental outcome of these patients. DESIGN AND METHODS The study included 21 Ashkenazi CH medically treated patients: 11 homozygotes (diffuse disease) and 9 heterozygotes with mutations on the paternal allele (presumed focal disease). The mean age was 13.7 years (range 8-23). Neurodevelopmental outcomes were assessed by telephone interviews of parents, using a standard questionnaire. Closest age siblings of CH patients served as controls. RESULTS Ten CH patients had perinatal seizures of short duration. Four had post-neonatal seizures, which remitted entirely. During early childhood, four patients (19%) had hypotonia, eight (38%) had fine motor problems, seven (33%) had gross motor problems (clumsiness), and one had mild cerebral palsy. Three patients (14%) had speech problems. Eight patients required developmental therapy, compared to one in the control group. Most of these problems were resolved by age 4-5 years. At school age, all were enrolled in regular education, some excelled in their studies, 6 out of 21 patients (29%) had learning problems (2 out of 21 controls). None had overt diabetes. CONCLUSIONS Good neurodevelopmental outcome was observed in our conservatively treated CH patients, with no diabetes as reported in patients undergoing pancreatectomy.

Insulin Resistance and Parental Obesity as Predictors to Response to Therapeutic Life Style Change in Obese Children and Adolescents 10 -18 Years Old

OBJECTIVE To study insulin resistance and parental obesity as predictors of improvement in weight status in obese children and adolescents undergoing therapeutic life change intervention (TLC). DESIGN A retrospective chart review. SUBJECTS One hundred thirty-four adolescents 10 to 18 years old above the 95th percentile for body mass index (BMI), referred to the Center for Atherosclerosis Prevention from January through December 2003. MEASUREMENTS BMI, fasting insulin, homeostasis model assessment insulin resistance (HOMA-IR). Weight management success was defined as BMI Z-score at final exam minus BMI Z-score at initial exam <or=0. Ninety-nine were successful (group S) (reduced or maintained BMI Z-score) and 35 were not successful (NotS) (increased BMI Z-score). RESULTS At baseline there were no differences between the groups in mean age, Tanner stage, gender, severity of obesity, lipid, and blood pressure levels. Insulin resistance was significantly higher in the NotS group compared to the S group as reflected by higher basal fasting insulin levels (21.8 +/- 12.3 vs. 15.8 +/- 9.0, p = .02), higher HOMA-IR (4.5 +/- 2.6 vs. 3.3 +/- 2.0, p = .02). After adjustment for age, gender, elevated blood pressure, abnormal lipid profile, baseline BMI Z-score, length of follow-up, and parental morbidity, an increase of 10 units of insulin resulted in a 3.13-fold (95% confidence interval [CI] 1.79-6.01) increased odds of failure. An increase in 1 unit of HOMA-IR resulted in 1.64-fold odds (95% CI 1.27-2.21) of failure. In the same multivariate logistic regression model the existence of obesity-associated morbidity in both parents was associated with 12.6-fold (95% CI 1.93-82.6) increased odds of failure. CONCLUSIONS Failing to respond to standard therapeutic lifestyle change intervention was dependent on baseline insulin resistance, and parental obesity-related comorbidity.