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Objective To compare the effectiveness of a single-layered polyethylene survival bag (P), a single-layered polyethylene survival bag with a hot drink (P+HD), a multi-layered metalized plastic sheeting survival bag (MPS: Blizzard Survival), and a multi-layered MPS survival bag with 4 large chemical heat pads (MPS+HP: Blizzard Heat) to treat cold casualties. Methods Portable cold casualty treatment methods were compared by examining core and skin temperature, metabolic heat production, and thermal comfort during a 3-hour, 0°C cold air exposure in 7 shivering, near-hypothermic men (35.4°C). The hot drink (70°C, ~400ml, ~28kJ) was consumed at 0, 1, and 2 hours during the cold air exposure. Results During the cold air exposure, core rewarming and thermal comfort were similar on all trials ( P = .45 and P = .36, respectively). However, skin temperature was higher (10%–13%; P d > 2.7) and metabolic heat production lower (15%–39%; P d > .9) on MPS and MPS+HP than P and P+HD. The addition of heat pads further lowered metabolic heat production by 15% (MPS+HP vs MPS; P = .05; large effect size d = .9). The addition of the hot drink to polyethylene survival bag did not increase skin temperature or lower metabolic heat production. Conclusions Near-hypothermic cold casualties are rewarmed with less peripheral cold stress and shivering thermogenesis using a multi-layered MPS survival bag compared with a polyethylene survival bag. Prehospital rewarming is further aided by large chemical heat pads but not by hot drinks.

OBJECTIVE To describe activity patterns in pregnant women with type 1 diabetes and evaluate the impact of increased structured physical activity on glucose control. RESEARCH DESIGN AND METHODS Physical activity energy expenditure (PAEE) and glucose levels (continuous glucose monitoring) were measured in 10 pregnant women with type 1 diabetes (age 33.2 years, gestation 20 weeks, BMI 27.9 kg/m2, diabetes duration 16.6 years, HbA1c 6.5% [48 mmol/mol], insulin pump duration 2.4 years) during a day at home (free-living) and during a 24-h visit incorporating controlled diet and structured physical activity with light intensity activity (three 20-min self-paced walks) and moderate intensity activity (two 50-min sessions of brisk treadmill walking). PAEE was evaluated through individually calibrated combined heart rate and movement sensing. RESULTS Free-living PAEE was comparable to that under controlled study conditions (3.8 and 5.1 kcal/kg/day, P = 0.241), with women achieving near to the recommended 30 min of moderate physical activity (median 27 min [interquartile range 14–68]). During the free-living period, more time was spent in light activity (10.3 vs. 7.2 h, P = 0.005), with less sedentary time (13.0 vs. 14.9 h, P = 0.047) and less moderate activity (27 vs. 121 min, P = 0.022). The free-living 24-h mean glucose levels by continuous glucose monitoring were significantly higher (7.7 vs. 6.0 mmol/L, P = 0.028). The effect of controlled diet and exercise persisted overnight, with significantly less time spent hyperglycemic (19 vs. 0%, P = 0.028) and less glucose variability (glucose SD 1.3 vs. 0.7 mmol/L, P = 0.022). CONCLUSIONS A controlled diet and structured physical activity program may assist women with type 1 diabetes in achieving optimal glucose control during pregnancy.

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic lipid species in muscle and elsewhere, impairing insulin action on glucose metabolism. Alternatively, however, defects in insulin signaling may be primary events that result in mitochondrial dysfunction, or there may be a bidirectional relationship between these phenomena. To investigate this, we examined mitochondrial function in patients with genetic defects in insulin receptor (INSR) signaling. We found that phosphocreatine recovery after exercise, a measure of skeletal muscle mitochondrial function in vivo, was significantly slowed in patients with INSR mutations compared with that in healthy age-, fitness-, and BMI-matched controls. These findings suggest that defective insulin signaling may promote mitochondrial dysfunction. Furthermore, consistent with previous studies of mouse models of mitochondrial dysfunction, basal and sleeping metabolic rates were both significantly increased in genetically insulin-resistant patients, perhaps because mitochondrial dysfunction necessitates increased nutrient oxidation in order to maintain cellular energy levels.

Resistance to thyroid hormone (RTH), a dominantly inherited disorder usually associated with mutations in thyroid hormone receptor beta (THRB), is characterized by elevated levels of circulating thyroid hormones (including thyroxine), failure of feedback suppression of thyrotropin, and variable tissue refractoriness to thyroid hormone action. Raised energy expenditure and hyperphagia are recognized features of hyperthyroidism, but the effects of comparable hyperthyroxinemia in RTH patients are unknown. Here, we show that resting energy expenditure (REE) was substantially increased in adults and children with THRB mutations. Energy intake in RTH subjects was increased by 40%, with marked hyperphagia particularly evident in children. Rates of muscle TCA cycle flux were increased by 75% in adults with RTH, whereas rates of ATP synthesis were unchanged, as determined by 13C/31P magnetic resonance spectroscopy. Mitochondrial coupling index between ATP synthesis and mitochondrial rates of oxidation (as estimated by the ratio of ATP synthesis to TCA cycle flux) was significantly decreased in RTH patients. These data demonstrate that basal mitochondrial substrate oxidation is increased and energy production in the form of ATP synthesis is decreased in the muscle of RTH patients and that resting oxidative phosphorylation is uncoupled in this disorder. Furthermore, these observations suggest that mitochondrial uncoupling in skeletal muscle is a major contributor to increased REE in patients with RTH, due to tissue selective retention of thyroid hormone receptor alpha sensitivity to elevated thyroid hormone levels.

Context: Lipodystrophy is a heterogeneous condition characterized by an inherited or acquired deficiency in the number of adipocytes required for the storage of energy as triglycerides. Acquired lipodystrophy is frequently associated with other autoimmune disorders. One well-studied form is characterized by the selective loss of upper body fat in association with activation of the alternative complement pathway by C3 nephritic factor, low complement factor C3, and mesangiocapillary glomerulonephritis. Objective: We now describe an immunologically distinct form of acquired generalized lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis. Patients and Research Design: Three unrelated patients with acquired lipodystrophy and low complement C4 levels are described. In vitro analysis of the complement pathway was undertaken to determine the reason for the low C4 complement levels. Biopsies were obtained from liver, bone marrow, and adipose tissue for histological analysis. Results: All three patients manifested near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels. Additional autoimmune diseases, including severe hemolytic anemia, autoimmune thyroid disease, and polyneuropathy, were variably present. Detailed studies of complement pathways suggested constitutive classical pathway activation. Conclusions: Although the previously described syndrome, which typically results in a cephalad pattern of partial lipodystrophy, results from activation of the alternative complement pathway, this form, in which lipodystrophy is generalized, is associated with activation of the classical pathway. Future therapeutic approaches to these disorders may benefit from being tailored to their distinct immunopathogenesis.

Background/objectives: The objective of this study was to develop approaches to expressing resting energy expenditure (REE) and lean body mass (LM) phenotypes of metabolic disorders in terms of Z-scores relative to their predicted healthy values. Subjects/methods: Body composition and REE were measured in 135 healthy participants. Prediction equations for LM and REE were obtained from linear regression and the range of normality by the standard deviation of residuals. Application is demonstrated in patients from three metabolic disorder groups (lipodystrophy, n=7; thyrotoxicosis, n=16; and resistance to thyroid hormone (RTH), n=46) in which altered REE and/or LM were characterised by departure from the predicted healthy values, expressed as a Z-score. Results: REE (kJ/min)=−0.010 × age (years)+0.016 × FM (kg)+0.054 × fat-free mass (kg)+1.736 (R2=0.732, RSD=0.36 kJ/min). LM (kg)=5.30 × bone mineral content (kg)+10.66 × height2 (m)+6.40 (male). LM (kg)=0.20 × fat (kg)+14.08 × height2 (m)−2.93 (female). (male R2=0.55, RSD=3.90 kg; female R2=0.59, RSD=3.85 kg). We found average Z-scores for REE and LM of 1.77 kJ/min and −0.17 kg in the RTH group, 5.82 kJ/min and −1.23 kg in the thyrotoxic group and 2.97 kJ/min and 4.20 kg in the LD group. Conclusion: This approach enables comparison of data from individuals with metabolic disorders with those of healthy individuals, describing their departure from the healthy mean by a Z-score.