Danièle Pacaud

Prevalence of overweight and obesity in children and adolescents with type 1 diabetes mellitus.

BACKGROUND Information about the prevalence of obesity in children with type 1 diabetes mellitus (DM1) is inconsistent and limited. The burden of the concurrent problems of obesity and DM1 can have notable medical, psychological, and social implications for both patients and their families. AIMS To determine prevalences of overweight and obesity in children with DM1 compared to a control population. METHODS In a cross-sectional study, we compared the prevalence of overweight/obesity in 390 children with DM1 (males 54%) and 565 controls (CONT; males 60%) aged 6 to 16 years. Overweight and obesity were defined as body mass indices between the 85th and 95th percentiles, and greater than the 95th percentile for age, respectively. RESULTS Overall, 29.5% DM1 and 18.1% CONT (p < 0.001) were either obese or overweight. The prevalence of obesity alone did not differ (DM1 5.4% vs CONT 8.2%), but a greater rate of overweight was seen in the DM1 group (DM 24.1% vs CONT 10.0%, p < 0.001). Rates of overweight were higher in the DM1 than CONT across all age groups and in both genders (males: DM1 20.1% vs CONT 8.9%, p < 0.001; females: DM1 28.7% vs CONT 11.5%, p < 0.001). Only females showed an increase in overall overweight/obesity rate (DM1 34.8% vs CONT 16.4%, p < 0.001) and this was most evident in older girls. CONCLUSIONS Children with DM1 are more overweight, but not more obese, than their nondiabetic counterparts. Additional research is warranted to evaluate the characteristics of DM1 and its management that may influence weight gain.

Normative Values for Corneal Nerve Morphology Assessed Using Corneal Confocal Microscopy: A Multinational Normative Data Set

OBJECTIVE Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS There was a significant linear age-dependent decrease in CNFD (−0.164 no./mm2 per year for men, P < 0.01, and −0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and −0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (−0.045 mm/mm2 per year, P = 0.07) and women (−0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

Comparison of conventional and non-invasive techniques for the early identification of diabetic neuropathy in children and adolescents with type 1 diabetes.

Background:  Neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. The availability of simple and non‐invasive tests for screening of early diabetic neuropathy (DN) in children with diabetes may prevent further progression of this complication. The purpose of this study was to compare conventional nerve conduction studies (NCS) with non‐invasive techniques, including vibration perception thresholds (VPT) and tactile perception thresholds (TPT) for the detection of DN in children and adolescents with type 1 diabetes.

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.

New insight into the pathophysiology of severe hypothyroidism in an infant with multiple hepatic hemangiomas

We report on an infant with severe acquired hypothyroidism resulting from both increased activity of type 3 iodothyronine deiodinase and increased production of TSH-like hormone from hepatic hemangiomas. The combination of these two mechanisms in a patient with hepatic hemangiomas has not been reported previously.

The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes

Husband AC, Crawford S, McCoy LA, Pacaud D. The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes.

Diabetic ketoacidosis and pediatric stroke

THE CASE: A 6-year-old previously healthy right-handed girl presented with a 3-day history of progressive epigastric abdominal pain, polydipsia and secondary nocturnal enuresis and a 2-week history of weight loss of 5 kg. Her initial assessment revealed tachypnea with Kussmauls respiration,

Pediatric stroke associated with new onset type 1 diabetes mellitus: case reports and review of the literature.

Abstract:  Neurological deterioration in children with diabetic ketoacidosis (DKA) is commonly caused by cerebral edema. However, stroke should also be suspected when focal neurological deficits are apparent, because children with hyperglycemia and DKA are prone to thrombosis. We report three cases of pediatric stroke associated with new onset type 1 diabetes mellitus (T1DM). The first case presented with sinovenous thrombosis, and the other two cases presented in DKA and had a late diagnosis of ischemic stroke following neurological deterioration. Our recent experiences and review of the literature emphasize the importance of early diagnosis, investigation, and treatment for patients that present with new onset T1DM and stroke.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Significance Congenital adrenal hyperplasia resulting from mutations in the CYP11B1 gene, which encodes a steroidogenic enzyme 11β-hydroxylase, is a rare inherited disorder associated with hyperandrogenemia, short stature, hypertension, and virilization of female newborns. We present a comprehensive clinical, genetic, and hormonal characterization for 68 of 108 patients with a genotype from an International Consortium on Rare Steroid Disorders. We also use computational modeling to define the effect of each of the missense mutations on the structure of 11β-hydroxylase, information that can be used to predict clinical severity prenatally in high-risk mothers. Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

Human endogenous retrovirus with a high genomic sequence homology with IDDMK1,2 22 is not specific for Type I (insulin-dependent) diabetic patients but ubiquitous

Aims/hypothesis. It has been reported recently that a novel human endogenous retroviral gene, insulin-dependent diabetes mellitus (IDDM)K1,222, was expressed in the plasma of Type I diabetic patients but not in that of nondiabetic control subjects. This investigation was initiated to determine the specificity of the selective expression of IDDMK1,222 in diabetic patients. Methods. We isolated the total RNA from the plasma and lymphocytes of 13 new onset Type I diabetic patients and 10 normal control subjects and amplified it by reverse transcriptase polymerase chain reaction. We then determined the presence of IDDMK1,222 with a specific primer set, U3/R-poly(A), used in a recent report and the 5 ′SAg/3 ′SAg primer set recognizing the putative superantigen encoding the region of the IDDMK1,222 envelope (env) gene. In addition, we carried out nested PCR of the U3/R-poly(A) polymerase chain reaction product using U3N/R primers. Results. We found no difference in the presence of the polymerase chain reaction products between diabetic patients and all nondiabetic subjects tested. Sequencing of the U3/R-poly(A) polymerase chain reaction products showed that the exact sequence of IDDMK1,222 was not present in any of the samples tested, neither in the plasma of diabetic patients nor in that of nondiabetic control subjects. Endogenous retroviral sequences with 90–93 % sequence homology to IDDMK1,222 were, however, equally present in both the diabetic and nondiabetic subjects. Conclusion/interpretation. We conclude that a human endogenous retroviral gene with high sequence homology with IDDMK1,222 is not specific for diabetic patients but, rather, is ubiquitous. [Diabetologia (1999) 42: 413–418]