The Dawn Phenomenon Revisited: Implications for Diabetes Therapy

ObjectiveTo summarize current data on the magnitude, prevalence, variability, pathogenesis, and management of the dawn phenomenon in patients with diabetes mellitus.MethodsOn the basis of the pertinent available literature and clinical experience, we propose a quantitative definition of the dawn phenomenon, discuss potential pathogenic mechanisms, and suggest management options.ResultsThe “dawn phenomenon” is a term used to describe hyperglycemia or an increase in the amount of insulin needed to maintain normoglycemia, occurring in the absence of antecedent hypoglycemia or waning insulin levels, during the early morning hours. To be clinically relevant, the magnitude of the dawn increase in blood glucose level should be more than 10 mg/dL or the increase in insulin requirement should be at least 20% from the overnight nadir. Controversy exists regarding the frequency, reproducibility, and pathogenesis of the dawn phenomenon. Approximately 54% of patients with type 1 diabetes and 55% of patients with type 2 diabetes experience the dawn phenomenon when the foregoing quantitative definition is used. The most likely pathogenic mechanism underlying the dawn phenomenon is growth hormone-mediated impairment of insulin sensitivity at the liver and muscles. The exact biochemical pathways involved are unknown. Therapeutic decisions aimed at correcting fasting hyperglycemia should take into account the variability and magnitude of the dawn phenomenon within individual patients. Successful insulinization appears to minimize the effects of the dawn phenomenon. Currently, no subcutaneous depot preparation of insulin exists that is capable of mimicking the basal insulinsecretion of the healthy pancreas.ConclusionIncreases in the bedtime doses of hypoglycemic agents with nighttime peaks in action may correct early morning hyperglycemia but be associated with undesirable nocturnal hypoglycemia. Targeted continuous subcutaneous insulin infusion programming can facilitate the prevention of early morning hyperglycemia in selected patients. (Endocr Pract. 2005;11:55-64)     

Nitroprusside Revisited

Sodium nitroprusside is a readily available, powerful hypotensive agent. It was administered intravenously in four cases when all other available hypotensive agents had failed, and blood pressure was controlled promptly and with no side effects. This is a valuable drug and deserves wider use.     

Asymmetry Revisited

Interest in the developmental basis of symmetry and asymmetry,as old as experimental embryology itself, has recently becomereactivated. A brief survey is made of recent or current activitiesin the following areas: (i) development of asymmetry in thechick limb bud, as related to the so-called zone of polarizingactivity (Saunders et al.); (ii) situs inversus viscerum inamphibians, as induced by transplantation and defect experiments,radiation, and chemical treatment (von Woellwarth, von Kraft,Wehrmaker); (iii) situs inversus viscerum in mammals as relatedto (a) twinning (Cockayne, Torgerson, Baker-Cohen); (b) genetics(Feldman, Cockayne, Torgerson for man, Tihen et al., Hummeland Chapman for mouse); and (c) teratogens (Layton and associates);(iv) ultrastructure in snails (Morrill and Perkins); (v) asymmetrydeveloping as a result of changes in chemical instability inhomogeneous systems (Ortoleva and Ross); (vi) asymmetrical mentality(Sperry and associates). No general conclusions are attempted.     

Lorenz Revisited

Certain characteristics of childhood immaturity (e.g., infantile facial features) may have been favored by natural selection to evoke positive feelings in adults. We propose that some aspects of cognitive immaturity might also endear young children to adults. In two studies, adults rated expressions of mature and immature thinking attributed to children. Immature thinking in which children expressed a supernatural explanation elicited positive affect reactions, whereas other forms of immature thinking, which made no attribution to supernatural causation, were responded to negatively. This pattern was found for parents and others, males and females, American and Spanish college students, and for target children 3 to 9 years of age. We suggest that persistence of supernatural thinking in adulthood causes people to view the expressions of such thinking in children in a positive manner, fostering nurturance of young children who display them.     

Androgenesis Revisited

Androgenesis can be defined as the set of biological processes leading to an individual genetically coming exclusively from a male nucleus. Androgenesis was traditionally considered as the spontaneous, in vivo development of a male-derived haploid embryo from a fertilized egg where the female nucleus is eliminated. However, at present it is also possible to generate androgenic haploids/doubled haploids through in vitro microspore embryogenesis and by in vitro meiocyte-derived callogenesis. These three androgenic alternatives clearly differ in the inducible stage, but lead to the same final haploid or doubled haploid product. Whereas microspore embryogenesis is widely studied and applied, the other two routes are much less known. In this paper, the evidence accounting for the existence of these three alternative pathways is revised, as well as the mechanisms potentially involved in their induction. Their differences and similarities are discussed from a biological perspective, leading to the notion that they might represent an ancient survival mechanism triggered by similar factors.     

Strongest Evidence Revisited

In response to comments by J. S. Farris (2000, Cladistics 16, 403–410) on the strongest evidence (SE) approach to phylogenetic analysis, I examine the concepts on which it is founded and reevaluate its merits. SE's null model of signal absence in characters is not treated as background knowledge, but as a reference point for evaluating a data set's phylogenetic signal in a tree-specific manner. In simulation tests, the SE methods perform reasonably well; although parsimony is generally more accurate and less biased than SE, SE is distinctly more accurate in some circumstances. Simulations further indicate that jackknifing is often beneficial in both SE and parsimony analyses. Iterative fixation of splits shows promise as an auxiliary procedure for SE and other methods that weight according to apparent homoplasy.