Arlan L. Rosenbloom

Limited Joint Mobility in Childhood Diabetes Mellitus Indicates Increased Risk for Microvascular Disease

We detected limited mobility of small and large joints in 92 (30 per cent) of 309 patients with diabetes who were one to 28 years old. Among patients who had had diabetes for more than 4.5 years (the shortest duration at which microvascular complications were noted), 82 of 169 had joint limitation. Forty-one of these 82 also had microvascular complications, but only 10 of the 87 patients without joint limitation had complications. Life-table analysis indicated an 83 per cent risk for microvascular complications after 16 years of diabetes if joint limitation was present, but only a 25 per cent risk if joint limitation was absent. Consequently, limited joint mobility identifies a population exceptionally at risk for the early development of microvascular complications, and intervention to forestall or prevent these complications can now be focused.

Intracerebral Crises During Treatment of Diabetic Ketoacidosis

Sixty-nine instances of intracerebral complications of diabetic ketoacidosis (DKA), including 29 unpublished occurrences, were analyzed to determine predictive factors, the frequency of other disorders resembling cerebral edema, the effectiveness of intervention to reduce intracranial pressure, and whether any etiologic considerations appeared valid. The review failed to implicate rate of hydration, tonicity of administered fluids, rate of correction of glycemia, or use of bicarbonate. Infants and young children (<5 yr of age) were disproportionately represented (33%), as were new-onset patients (62%). Approximately 20% of patients were found to have localized basilar edema, hemorrhage, thromboses, or infection by computed tomography scan or on postmortem examination. The histories of 50% of the patients suggested a period of dramatic neurological change preceding respiratory arrest (RA) during which intervention might be effective. Twenty-three patients were treated for increased intracranial pressure before RA; 13 patients survived in an independent functional state, and 3 survived in a severely disabled or vegetative state. Only 3 of the remaining 46 patients survived normally: 2 were untreated and never developed RA, and 1 was given mannitol at the onset of apnea. This review supports close neurological monitoring and intervention to reduce intracranial pressure when there are definite signs of neurological compromise. However, treatment appears to be successful in only 50% of patients who give sufficient warning for such intervention, and they comprised half of the study population. Therefore, prevention of DKA remains the most important goal to avoid intracerebral complications.

Diabetic ketoacidosis in children and adolescents with diabetes

aDivision of Endocrinology, Children’s Hospital Boston, MA, USA; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cUniversity of Toronto, The Hospital for Sick Children, Toronto, Canada; dDepartment of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; eDepartment of Paediatrics, John Radcliffe Hospital, Oxford, UK; fEndocrinology Service Department of Paediatric Medicine, KK Children’s Hospital, Singapore; gDivision of Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; hDepartment of Pediatric Endocrinology, Children’s Hospital, University of Pittsburgh, PA, USA; iDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden

Influence of Race, Ethnicity, and Culture on Childhood Obesity: Implications for Prevention and Treatment: A consensus statement of Shaping America's Health and the Obesity Society

Obesity may be thought of as a body weight that conveys significant risk for adverse health outcomes. In children, obesity is defined as a BMI at or above the 95th percentile for age and sex, based on population data from the 1970s (1,2). The prevalence of obesity has increased markedly in U.S. children and adolescents in the past 30 years. Obesity-related risk factors and diseases formerly seen only in adults are increasingly being recognized in obese adolescents and even younger children. Race and ethnicity are terms used to categorize populations on the basis of shared characteristics. Race has traditionally been used to categorize populations on the basis of shared biological characteristics such as genes, skin color, and other observable features. Ethnicity is used to categorize on the basis of cultural characteristics such as shared language, ancestry, religious traditions, dietary preferences, and history. Although ethnic groups can share a range of phenotypic characteristics due to their shared ancestry, the term is typically used to highlight cultural and social characteristics instead of biological ones (3). Both race and ethnicity are, in fact, social constructs. The assumption that race reflects only biological distinctions is inaccurate. Categories based on race account for only 3–7% of total human genetic diversity, are not reliably measured, and are not always biologically meaningful (3,4). Furthermore, both race and ethnicity are constantly evolving concepts, making the task of comparing groups or following the same group over time quite challenging. For instance, the increasing proportion of the U.S. population describing their race as “mixed” or “other,” as well as changes in ethnic self-identification across generations and occasionally even within the same generation, makes it difficult to assign individuals to invariant categories of race or ethnicity. Nevertheless, the social importance given to these constructs to describe …

Thyroid autoimmunity in insulin-dependent diabetes mellitus: The case for routine screening

Of 771 young diabetic patients, thyroid microsomal autoantibodies occurred in 136 (17.6%) at a female/male ratio of nearly 2:1 and with a predominance of white patients (20.1%) over black patients (5.5%) (P less than 0.001). Thus, one in every four white female patients with insulin-dependent diabetes mellitus had TMA. Thyroglobulin autoantibodies were no more common in patients with IDDM than among controls. Of the 117 patients (out of the 136) with serologic evidence of chronic thyroiditis who could be studied, eight (7%) had hyperthyroidism and 45 (38%) were hypothyroid. Hyperthyroidism usually preceded or coincided with the appearance of IDDM, whereas hypothyroidism occurred with or following the onset of IDDM. Hypothyroidism appeared irreversible in most patients, but in three, periods of hypothyroidism were followed by euthyroidism, presumably explained by a compensatory hyperplasia of the thyroid gland. In the 136 patients with TMA, gastric and adrenocortical autoantibodies also occurred at relatively high frequencies (16.8% and 5.1%, respectively). On the basis of these studies, we urge that all patients with IDDM be screened for TMA and that those with positive results undergo annual thyroid function tests as well as determinations of gastric parietal and adrenocortical autoantibodies.

Influence of Race, Ethnicity, and Culture on Childhood Obesity: Implications for Prevention and Treatment

Obesity may be thought of as a body weight that conveys significant risk for adverse health outcomes. In children, obesity is defined as a BMI at or above the 95th percentile for age and sex, based on population data from the 1970s (1,2). The prevalence of obesity has increased markedly in US children and adolescents in the past 30 years. Obesity-related risk factors and diseases formerly seen only in adults are increasingly being recognized in obese adolescents and even younger children. Race and ethnicity are terms used to categorize populations on the basis of shared characteristics. Race has traditionally been used to categorize populations on the basis of shared biological characteristics such as genes, skin color, and other observable features. Ethnicity is used to categorize on the basis of cultural characteristics such as shared language, ancestry, religious traditions, dietary preferences, and history. Although ethnic groups can share a range of phenotypic characteristics due to their shared ancestry, the term is typically used to highlight cultural and social characteristics instead of biological ones (3). Both race and ethnicity are, in fact, social constructs. The assumption that race reflects only biological distinctions is inaccurate. Categories based on race account for only 3–7% of total human genetic diversity, are not reliably measured, and are not always biologically meaningful (3,4). Furthermore, both race and ethnicity are constantly evolving concepts, making the task of comparing groups or following the same group over time quite challenging. For instance, the increasing proportion of the US population describing their race as “mixed” or “other,” as well as changes in ethnic selfidentification across generations and occasionally even within the same generation, makes it difficult to assign individuals to invariant categories of race or ethnicity. Nevertheless, the social importance given to these constructs to describe groups that have been treated in similar ways based on presumed biological characteristics, as well as the acknowledgment that such classifications themselves have contributed to inequalities in health and health care access, necessitates that we continue to use the terms race and ethnicity. Although childhood obesity is increasing in all ethnic and racial groups, its prevalence is higher in non-white populations. The reasons for the differences in prevalence of childhood obesity among groups are complex, likely involving genetics, physiology, culture, socioeconomic status (SES), environment, and interactions among these variables as well as others not fully recognized. Understanding the influence of these variables on the patterns of eating and physical activity that lead to obesity will be critical to developing public policies and effective clinical interventions to prevent and treat childhood obesity. To address the evidence base and gaps in knowledge in this area, Shaping America’s Health and the Obesity Society convened a consensus development conference on 9–11 April 2008. Following presentations by invited speakers and in-depth discussions, a seven-member panel of experts in pediatric endocrinology, cardiology, gastroenterology, nutrition, epidemiology, and anthropology developed this consensus statement on the influence of race, ethnicity, and culture on childhood obesity, addressing the following questions:

Joint contracture—common manifestation of childhood diabetes mellitus

Sixty-five of 229 seven to eighteen-year-old campers with diabetes were found to have contractures of finger joints; in two thirds of affected children only the fifth finger was involved. Stiff resistance to passive finger manipulation and thickened adherent skin over the dorsa of the hands were additional features. Short stature was associated with involvement of more than one finger; the shortest youngsters also had contractures of large joints. Joint changes were independent of age, sex, age of onset of diabetes, and control of diabetes, but correlated with duration of the diabetes.

Diabetic ketoacidosis and hyperglycemic hyperosmolar state

aDivision of Endocrinology, Boston Children’s Hospital, Boston, MA, USA; bBarts Health NHS Trust, Royal London Hospital, London, UK; cInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead; School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; dOxfordshire Children’s Diabetes Service, Oxford Children’s Hospital, Oxford, UK; eSection of Endocrinology, University of California, Davis School of Medicine, Sacramento, CA, USA; fPediatric Endocrinology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India; gEndocrinology Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore; hDepartment of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya ; iDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; jDivision of Endocrinology, Diabetes and Metabolism, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA and kDepartment of Pediatrics, NU Hospital Group, Uddevalla and Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden

Islet Cell and Other Organ-specific Antibodies in U.S. Caucasians and Blacks with Insulin-dependent Diabetes Mellitus

SUMMARY Islet cell antibodies (ICA) were detected in 168 (33%) of 504 patients with insulin-dependent diabetes mellitus (IDDM). Mean age of onset of IDDM was 8.6 ± 0.2 yr and mean age at testing was 13.4 ± 0.3 yr. None of 162 controls without diabetes (mean age 21.8 ± 0.9 yr) had ICA. Caucasian patients (404) had a 74% frequency of ICA within 3 mo of diagnosis and an overall ICA frequency of 36%. These results were similar to those reported from Europe. Black patients (100) had lower frequencies of ICA (P < 0.01) and thyroid antibodies (P < 0.05). Caucasian patients with onset of IDDM before 5 yr of age (107) had a lower frequency (P < 0.01) of ICA (21%) than those (297) with a later age of onset (42%). Patients with persistent ICA beyond 5 yr of IDDM had increased frequencies of gastric parietal and adrenal cortex cell antibodies. Thyroid microsomal antibodies were less frequent (P < 0.05) in blacks (4%) than in Caucasians (20%). The former did not have adrenal antibodies. Similar ICA frequencies among Caucasians with IDDM in the U.S. and in Europe suggest that etiologie factors are similar in the two geographic regions. The lower frequencies of ICA in patients with IDDM onset before 5 yr of age suggest that some of these patients may have a different etiology and/or a more rapid disappearance of islet cell antigens than patients with a later onset. The lower ICA frequencies in black patients can be explained by heterogeneity of IDDM in this group and by admixture of IDDM susceptibility genes from the Caucasian genome to the black genome.

CONNECTIVE TISSUE AND JOINT DISEASE IN DIABETES MELLITUS

Connective tissue is ubiquitous and subject to alterations that result in changes in the extracellular matrix of vessels and tissues leading to the long-term complications of diabetes. This article reviews only those abnormalities of interstitial connective tissue involving skeleton, joints, skin, and periarticular tissues. Abnormalities in the skin and periarticular tissues result in syndromes limiting joint movement, including limited joint mobility, Dupuytren disease, flexor tenosynovitis, carpal tunnel syndrome, stiff-hand syndrome, and shoulder-hand reflex dystrophy. Of these, only limited joint mobility and stiff-hand syndrome occur exclusively in patients with diabetes. In all of these conditions, advanced glycation end products are thought to form as a result of nonenzymatic reaction of glucose with proteins, causing stiffening.