Key Global Literature

  1. Vivian Fonseca, MD
  1. Division of Endocrinology, Tulane University Medical Center, New Orleans, Louisiana. E-mail: vfonseca{at}

    Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM: Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503, 2001

    Findings. All pregnant women (n = 12,055) in northern Finland who were due to give birth in 1966 were enrolled in this birth-cohort study. Data were collected in the first year of life about frequency and dose of vitamin D supplementation, the presence of suspected rickets, and a diagnosis of type 1 diabetes during the first year of life. Of the 10,366 children included in analyses, 81 were diagnosed with diabetes during the study. Vitamin D supplementation was associated with a decreased frequency of type 1 diabetes when adjusted for neonatal, anthropometric, and social characteristics (rate ratio [RR] for supplementation 0.12, 95% CI 0.03–0.51), and irregular versus no supplementation (0.16, 0.04–0.74). Children who regularly took the recommended dose of vitamin D (2,000 IU daily) had an RR of 0.22 (0.05–0.89) compared with those who regularly received less than the recommended amount. Children suspected of having rickets during the first year of life had an RR of 3.0 (1.0–9.0) compared with those without such a suspicion.

    Significance. Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes in animals, and vitamin D has effects on the immune system in humans. Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes.

    Clinical impact. Ensuring adequate vitamin D supplementation for infants in order to prevent rickets is logical. Perhaps it may have the added benefit of reversing the increasing trend in the incidence of type 1 diabetes. With the lack of success of immunological approaches to prevention of type 1 diabetes, clinical trials are in need of such approaches in older children who are identified as being at high risk for the disease. In the meantime, it makes sense to follow appropriate recommendations for vitamin intake for all children.

    Collins AC, Vincent J, Newall RG, Mitchell KM, Viberti GC: An aid to the early detection and management of diabetic nephropathy: assessment of a new point of care microalbuminuria system in the diabetic clinic. Diabet Med 18:928–932, 2001

    Findings. Collins et al. compared the performance of a “point of care” instrument in a diabetes clinic—the DCA2000 microalbuminuria system for urine albumin and creatinine concentrations and the albumin-to-creatinine ratio (ACR) with laboratory measurements. Diabetic and normal subjects were studied. They also assessed the ease of use and applicability of the instrument by standard clinic personnel. Both albumin assays are based on immunoturbidimetry. The DCA2000 system utilizes reagent cartridges processed automatically, with results available immediately. Control material within-run precision (coefficient of variation [CV]) for albumin and creatinine ranged up to 7.1 and 3.3%, respectively. Between-run CVs ranged from 2.1 to 4.3%. The correlation coefficients between methods was >0.99 for albumin, creatinine, and ACR, with only a small negative bias of 3.2 mg/l for albumin and 0.10 mg/mmol for ACR; there was no concentration-related bias for ACR and no between-method difference for either albumin or ACR. The sensitivity, specificity, and negative and positive predictive values were 92.4, 100, 92.7, and 100%. Clinic personnel found that the DCA2000 system was easy to use, suited the clinic environment, and generated confidence in the results.

    Significance. Studies have demonstrated that despite its value and the recommendations of organizations like the American Diabetes Association, microalbuminuria testing is frequently not carried out in practice. Furthermore, physicians often do not act on an abnormal test result until the patient returns for the next visit, which may be several months later. This point of care system safely substitutes laboratory-based measurements. Ease of use and low cost make it suitable for screening and monitoring diabetes treatment.

    Clinical impact. Potentially huge. I agree with the authors, who conclude that this approach has a clear place in clinical practice.

    Schoenle EJ, Schoenle D, Molinari L, Largo RH: Impaired intellectual development in children with type I diabetes: association with HbA1c, age at diagnosis, and sex. Diabetologia 45:108–114, 2002

    Findings. Schoenle et al. carried out a prospective longitudinal study to evaluate the role of long-term metabolic control and hypoglycemia in affecting the intellectual development of young children with type 1 diabetes. Intellectual development in 64 diabetic children and age-matched healthy control subjects between the ages of 7 and 16 years was assessed at least four times using the German version of the Hamburg Wechsler intelligence scale for preschool children, Children-Revised and by the “Adaptives Intelligenz Diagnostikum” (Adaptive Intelligence Diagnosticum). Data were analyzed longitudinally compared with a control group. A significant decline in performance by age 7 and in verbal intelligence quotient between age 7 and 16 years was observed in diabetic boys diagnosed before the age of 6, but not in those diagnosed later and not in girls. The deterioration of intellectual performance in these boys was not associated with the occurrence of severe hypoglycemic episodes, but was correlated with the degree of metabolic deterioration at diagnosis and with high long-term average of glycated hemoglobin.

    Significance. Good metabolic control in diabetic children may prevent diabetic complications later in life. However, physicians and patients’ parents are frequently afraid that tight metabolic control could increase the risk of severe hypoglycemia, which might be responsible for impaired intellectual performance later in life. However, the basis for such a fear has never been demonstrated in prospective studies. In the Diabetes Control and Complications Trial, which was carried out in adolescents and not young children, there was no deterioration in intellectual function associated with intensive therapy. This study in diabetic children shows that the male sex, diagnosis at a young age, metabolic condition at diagnosis, and long-term metabolic control, rather than hypoglycemia, are risk factors for impairment in intellectual development.

    Clinical impact. This study challenges “conventional wisdom” and needs to be confirmed in a larger study. If confirmed, it may lead to reassurance of health care providers about the perceived fears related to hypoglycemia and could thus lead to better control of diabetes in children and reduction in long-term complications.

    Leggetter S, Chaturvedi N, Fuller JH, Edmonds ME: Ethnicity and risk of diabetes-related lower extremity amputation: a population-based, case-control study of African Caribbeans and Europeans in the United Kingdom. Arch Intern Med 162:73–78, 2002

    Findings. This was an incidence and case-control study carried out in London, England. All diabetes-related amputations performed between 1992 and 1997 were identified. Control subjects were patients with diabetes who did not have an amputation. Risk factor data were abstracted from medical records. Incident diabetes-related amputation occurred in 67 Europeans and 19 African Caribbeans. Amputation rates, age standardized to the diabetic population, were 147 per 100,000 and 219 per 100,000 in African Caribbeans and Europeans, respectively. The difference between groups was not statistically significant (RR 0.67, 95% CI 0.32–1.40). Case-control analyses were performed on 178 case subjects and 350 control subjects. The ethnic difference in amputation risk differed significantly by sex (P = 0.009 for interaction). The unadjusted odds ratio was lower in African Caribbean men compared with European men (0.31, 0.17–0.57; P < 0.001). There were no differences between the ethnic groups in women. Adjustment for smoking, neuropathy, peripheral vascular disease, and age attenuated the odds ratio to 0.97, which was not statistically significant.

    Significance. In the U.S., African-Americans with diabetes have two to three times the amputation risk of Caucasian diabetic individuals. The reason for this excess is not clear and may be due to differences in care or genetic or patho-physiological characteristics. In the U.K., health care delivery is reported to be more equitable for all ethnic groups. In contrast to the U.S., this study found no ethnic difference in diabetes-related amputation in women in the U.K. Surprisingly, in men, amputation risk in African Caribbeans was one third that of Europeans, although this difference was probably accounted for by low smoking, neuropathy, and peripheral vascular disease rates.

    Clinical impact. These data should prompt health care policy makers to examine the impact of inequalities in access to quality care to some sections of the population. High amputation rates in African-American diabetic individuals have significant social and economic costs.

    Guazzi M, Brambilla R, Pontone G, Agostoni P, Guazzi MD: Effect of non-insulin-dependent diabetes mellitus on pulmonary function and exercise tolerance in chronic congestive heart failure. Am J Cardiol 89:191–197, 2002

    Findings. Guazzi et al. tested the hypothesis that coexistence of non–insulin-dependent diabetes mellitus (NIDDM) may potentiate the deterioration of lung function in congestive heart failure (CHF). They investigated cardiac function, pulmonary volumes, carbon monoxide diffusion [DL(CO)] and its alveolar-capillary membrane [D(M)] subcomponent, oxygen uptake and dead space-to-tidal volume ratio (pVD/VT) at peak exercise (individualized ramp test), and slope of ventilation-to-carbon dioxide production ratio [VE/VCO(2)] during exercise in 20 patients without diabetes (group 1) and in 20 patients with type 2 diabetes (group 2), and also studied 20 age- and gender-matched control subjects. Both patient groups had New York Heart Association class II to III CHF due to idiopathic or ischemic cardiac disease. Compared with control subjects, both patient groups had similar abnormalities in left ventricular diastolic volume, ejection fraction, and pulmonary wedge pressure. In patients with diabetes, lung volumes, DL(CO), D(M), and oxygen uptake were significantly more reduced compared with non-diabetic subjects. Furthermore, VE/VCO(2) slope and pVD/VT also were significantly increased and inversely correlated with D(M).

    Significance. Very little is known about the impact of diabetes on pulmonary function. In contrast, “diabetic cardiomyopathy” is well recognized, as is the fact that patients with diabetes have more severe CHF and poorer outcomes. This study demonstrates that the coexistence of diabetes makes pulmonary dysfunction worse in CHF and significantly enhances exercise intolerance.

    Clinical impact. These data, though preliminary and derived from a small number of patients, provide us with an explanation for the more severe CHF symptoms in some of our patients. If confirmed, further studies will be needed to determine whether therapy directed toward improving pulmonary function is needed in patients with diabetes and CHF.


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