A high linear growth is associated with an increased risk of childhood diabetes mellitus

Summary Insulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recentonset diabetic children, 0–14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to 1 years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values <0; 0–1 and > 1, respectively; p=0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found. Weight-for-height was similar among diabetic and referent children of both sexes. We conclude that diabetic boys tend to be taller and grow faster than referent boys for several years preceding the disease. A similar, but not statistically significant tendency was found among diabetic girls. Our findings indicate that rapid linear growth is a risk factor for Type 1 diabetes in childhood, and may be either a promoter of Type 1 diabetes or else a marker of a physiological mechanism that affects both growth and the pathogenesis of Type 1 diabetes.     

Hermeneutic reading of classic texts

The purpose of this article is to broaden the understandinfg of the hermeneutic reading of classic texts. The aim is to show how the choice of a specific scientific tradition in conjunction with a methodological approach creates the foundation that clarifies the actual realization of the reading. This hermeneutic reading of classic texts is inspired by Gadamer's notion that it is the researcher's own research tradition and a clearly formulated theoretical fundamental order that shape the researcher's attitude towards texts and create the starting point that guides all reading, uncovering and interpretation. The researcher's ethical position originates in a will to openness towards what is different in the text and which constantly sets the researcher's preunderstanding and research tradition in movement. It is the researcher's attitude towards the text that allows the text to address, touch and arouse wonder. Through a flexible, lingering and repeated reading of classic texts, what is different emerges with a timeless value. The reading of classic texts is an act that may rediscover and create understanding for essential dimensions and of human beings' reality on a deeper level. The hermeneutic reading of classic texts thus brings to light constantly new possibilities of uncovering for a new envisioning and interpretation for a new understanding of the essential concepts and phenomena within caring science.     

Clues for early detection of autoimmune Addison's disease – myths and realities

Background

Early detection of autoimmune Addison's disease (AAD ) is important as delay in diagnosis may result in a life‐threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well‐described, but methodical investigations are scarce.

Objective

Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD .

Material and Methods

A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978–2016. Scrutiny of medical records provided patient data and laboratory values.

Results

Low sodium occurred in 207 of 247 (84%), but only one‐third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty‐three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L^?1 [1–668]) and significantly lower in individuals with adrenal crisis (38 nmol L^?1 [2–442]) than in those without (81 nmol L^?1 [1–668], P < 0.001).

Conclusion

The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD , and on clinical suspicion bring about assay of cortisol and ACTH . Presence of 21‐hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

     

Dendritic Cells in Bone Marrow at Diagnosis and after Chemotherapy in Adult Patients with Acute Myeloid Leukaemia

Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitor cells. Two subsets, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), have been identified. Little is known regarding DC levels in bone marrow of patients with acute myeloid leukaemia (AML) before and after chemotherapy. We investigated relative pDC and mDC levels in bone marrow from 37 hospital controls and 60 patients with AML [at diagnosis, complete remission (CR) and follow‐up] using four‐colour flow cytometry. The pDC immunophenotype was characterized as lin‐/HLA‐DR+/CD123 +  and mDC as lin‐/HLA‐DR+/CD11c+. In 69% of patients with AML, no DCs were detected at diagnosis. At CR, mDC levels were the same in patients with AML and hospital controls while pDC levels were slightly lower. There was no association between minimal residual disease or survival rates and DC levels. Patients with low mDC levels at CR were more likely to suffer from complicated infections, although the difference was not statistically significant. Altogether, there was a profound decrease in DC levels in patients with AML at diagnosis. DC levels increased at CR and were higher than in hospital controls after post‐remission therapy, suggesting that DCs recover after repeated chemotherapy. There may be an association between mDC levels and infectious complications.     

Influence of anoxia on glucose metabolism in pancreatic islets: Lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux

Summary When equilibrated with O₂-CO₂ (95:5), pancreatic islets of non-inbredob/ob-mice exhibited a sigmoidal dependence of³H₂O production on D-(5-³H)-glucose concentration; the rate was most sensitive to changes of glucose concentration around 5mM and tended to be maximum above about 15 mM glucose.³H₂O production from more than 5 mM D-(5-³H)-glucose was about twice as fast as the production of¹⁴CO₂ from equimolar D-(U-¹⁴C)-glucose. Islets equilibrated with N₂-CO₂ (95:5) did not exhibit a sigmoidal dose-response curve for³H₂O production, the process being inhibited by anoxia at glucose concentrations above 5mM. Pieces of exocrine pancreas had a slower aerobic³H₂O production than the islets and showed a clear enhancement of the process during anoxia. In comparison with oxygenated islets, anoxic islets exhibited decreased concentrations of glucose-6-phosphate and increased concentrations of fructose-l,6-diphosphate. The concomitant inhibition of glycolytic flux may be due to a low lactate dehydrogenase activity in islets yielding a slow reoxidation of NADH and a slow phosphoglyceraldehyde oxidation under anaerobic conditions.     

Rose Hip and Lactobacillus plantarum DSM 9843 Reduce Ischemia/Reperfusion Injury in the Mouse Colon

Ischaemia/reperfusion (I/R) of the colon is an inflammatory condition that leads to tissue injury where reactive oxygen species play a central role. Rose hip is rich in biologically active polyphenols with antioxidative properties, which may be important in prevention of lipid peroxidation. L. plantarum DSM 9843 possesses enzymatic activity towards polyphenols. The objective of this study was to define the effect of oral administration of L. plantarum and rose hip in I/R injury. Administration of rose hip and L. plantarum significantly decreased MDA levels in caecum tissue and Enterobacteriaceae counts in caecum stool. A positive correlation between MDA levels and Enterobacteriaceae counts was found. The results support a synergistic/additive role of rose hip and L. plantarum in reducing lipid peroxidation. Therefore rose hip and L. plantarum may be used as a pretreatment to tissue injuries, e.g. colonic surgery, organ transplantation and vascular surgery.     

Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

Aims/hypothesis We used oestrogen receptor-α (ERα) knockout (ERKO) and receptor-β (ERβ) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. Methods Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic–hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding steroyl-CoA desaturase and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. Results ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemic–hyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. Conclusions/interpretation We conclude that oestrogens, acting via ERα, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.     

Chronic daily headache with medication overuse: a randomized follow-up by neurologist or PCP

Several studies have shown the benefit of withdrawal therapy when medication overuse headache (MOH) is suspected. Our aim was to compare the effect of withdrawal therapy in patients followed by a neurologist (group A, n  = 42) and a primary care physician (PCP) (group B, n  = 38). Patients were randomized to A or B, and follow-up was at 3, 6 and 12 months. Calculated mean headache (MH at 6 months + MH at 12 months)/2 (primary end-point) was similar; A 1.04 (0.87, 1.21) and B 1.02 (0.82, 1.21) ( P  = 0.87). The number of patients with 50% improvement of headache days was also similar; 14/42 in group A vs. 12/34 in B ( P  = 0.86) at 3 months, 15/42 vs. 11/33 ( P  = 0.83) at 6 months and 15/42 vs. 14/38 ( P  = 0.92) at 12 months. Days without headache during the last 9 months of follow-up were 123 (96, 150) in group A and 137 (112, 161) in B ( P  = 0.62). After 3 months one-third were classified as MOH. Patients with MOH improved similarly in group A and B, and so did patients without MOH. Within 1 year 7/42 in A and 9/38 in B had recurrent medication overuse ( P  = 0.43). In summary, there were no significant differences in follow-up results between the two groups.