Vitamin D status is known to be poor in obese individuals; there is no consensus as to the reason. Cross‐sectional study of the relation between serum 25‐hydroxyvitamin D (25(OH)D) concentration and body size in the baseline data from unsupplemented adults entering two study cohorts in our research unit, N = 686. Regression analyses of body size variables against serum 25(OH)D concentration, using both linear and hyperbolic models. The fit to a hyperbolic model of 25(OH)D against body weight completely removed the obesity‐related component of inter‐individual variability in serum 25(OH)D concentration. The hyperbolic fit using total body weight was significantly better than any linear model, and specifically better than any using BMI. Dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients fully explains their typically low vitamin D status. There is no evidence for sequestration of supplemental or endogenous cholecalciferol. Vitamin D replacement therapy needs to be adjusted for body size if desired serum 25(OH)D concentrations are to be achieved.

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Abstract-Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling pathways was undertaken in primary cultures of cardiac myocytes, a cell type that is especially sensitive to ischemia-induced apoptosis. Deprivation of serum and glucose, components of ischemia in vivo, resulted in myocyte apoptosis, as determined by nuclear fragmentation, internucleosomal cleavage of DNA, and processing of caspase substrates. These manifestations of apoptosis were blocked by zVAD-fmk, a peptide caspase inhibitor, indicating that caspase activity is necessary for the progression of apoptosis in this model. In contrast to control cells, apoptotic myocytes exhibited cytoplasmic accumulation of cytochrome c, indicating release from the mitochondria. Furthermore, both caspase-9 and caspase-3 were processed to their active forms in serum-/glucose-deprived myocytes. Caspase processing, but not cytochrome c release, was inhibited by zVAD-fmk, placing the latter event upstream of caspase activation. This evidence demonstrates that components of ischemia activate the mitochondrial death pathway in cardiac myocytes. (Circ Res. 1999;85:403-414.)

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The pandemic of COVID-19 has presented new challenges to hospital personnel providing care for infected patients with diabetes who represent more than 20% of critically ill patients in intensive care units. Appropriate glycemic management contributes to a reduction in adverse clinical outcomes in acute illness but also requires intensive patient interactions for bedside glucose monitoring, intravenous and subcutaneous insulin administration, as well as rapid intervention for hypoglycemia events. These tasks are required at a time when minimizing patient interactions is recommended as a way of avoiding prolonged exposure to COVID-19 by health care personnel who often practice in settings with limited supplies of personal protective equipment. The purpose of this manuscript is to provide guidance for clinicians for reconciling recommended standards of care for infected hospitalized patients with diabetes while also addressing the daily realities of an overwhelmed health care system in many areas of the country. The use of modified protocols for insulin administration, bedside glucose monitoring, and medications such as glucocorticoids and hydroxychloroquine that may affect glycemic control are discussed. Continuous glucose monitoring systems have been proposed as an option for reducing time spent with patients, but there are important issues that need to be addressed if these are used in hospitalized patients. On site and remote glucose management teams have potential to provide guidance in areas where there are shortages of personnel who have expertise in inpatient glycemic management.

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Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).

Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone micro-architecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex- matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 micron resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. 1988.[1] Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility.