It is not uncommon for people to spend one-half of their waking day sitting, with relatively idle muscles. The other half of the day includes the often large volume of nonexercise physical activity. Given the increasing pace of technological change in domestic, community, and workplace environments, modern humans may still not have reached the historical pinnacle of physical inactivity, even in cohorts where people already do not perform exercise. Our purpose here is to examine the role of sedentary behaviors, especially sitting, on mortality, cardiovascular disease, type 2 diabetes, metabolic syndrome risk factors, and obesity. Recent observational epidemiological studies strongly suggest that daily sitting time or low nonexercise activity levels may have a significant direct relationship with each of these medical concerns. There is now a need for studies to differentiate between the potentially unique molecular, physiologic, and clinical effects of too much sitting (inactivity physiology) separate from the responses caused by structured exercise (exercise physiology). In theory, this may be in part because nonexercise activity thermogenesis is generally a much greater component of total energy expenditure than exercise or because any type of brief, yet frequent, muscular contraction throughout the day may be necessary to short-circuit unhealthy molecular signals causing metabolic diseases. One of the first series of controlled laboratory studies providing translational evidence for a molecular reason to maintain high levels of daily low-intensity and intermittent activity came from examinations of the cellular regulation of skeletal muscle lipoprotein lipase (LPL) (a protein important for controlling plasma triglyceride catabolism, HDL cholesterol, and other metabolic risk factors). Experimentally reducing normal spontaneous standing and ambulatory time had a much greater effect on LPL regulation than adding vigorous exercise training on top of the normal level of nonexercise activity. Those studies also found that inactivity initiated unique cellular processes that were qualitatively different from the exercise responses. In summary, there is an emergence of inactivity physiology studies. These are beginning to raise a new concern with potentially major clinical and public health significance: the average nonexercising person may become even more metabolically unfit in the coming years if they sit too much, thereby limiting the normally high volume of intermittent nonexercise physical activity in everyday life. Thus, if the inactivity physiology paradigm is proven to be true, the dire concern for the future may rest with growing numbers of people unaware of the potential insidious dangers of sitting too much and who are not taking advantage of the benefits of maintaining nonexercise activity throughout much of the day.

https://diabetes.diabetesjournals.org/content/diabetes/56/11/2655.full.pdf

Role of Low Energy Expenditure and Sitting in Obesity, Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease

KATZMARZYK, P. T., T. S. CHURCH, C. L. CRAIG, and C. BOUCHARD. Sitting Time and Mortality from All Causes, Cardiovascular Disease, and Cancer. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 998–1005, 2009. Purpose: Although moderate-tovigorous physical activity is related to premature mortality, the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise. We prospectively examined sitting time and mortality in a representative sample of 17,013 Canadians 18–90 yr of age. Methods: Evaluation of daily sitting time (almost none of the time, one fourth of the time, half of the time, three fourths of the time, almost all of the time), leisure time physical activity, smoking status, and alcohol consumption was conducted at baseline. Participants were followed prospectively for an average of 12.0 yr for the ascertainment of mortality status. Results: There were 1832 deaths (759 of cardiovascular disease (CVD) and 547 of cancer) during 204,732 person-yr of follow-up. After adjustment for potential confounders, there was a progressively higher risk of mortality across higher levels of sitting time from all causes (hazard ratios (HR): 1.00, 1.00, 1.11, 1.36, 1.54; P for trend G0.0001) and CVD (HR: 1.00, 1.01, 1.22, 1.47, 1.54; P for trend G0.0001) but not cancer. Similar results were obtained when stratified by sex, age, smoking status, and body mass index. Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87, 86, 105, 130, and 161 (P for trend G0.0001) in physically inactive participants and 75, 69, 76, 98, 105 (P for trend = 0.008) in active participants across sitting time categories. Conclusions: These data demonstrate a dose–response association between sitting time and mortality from all causes and CVD, independent of leisure time physical activity. In addition to the promotion of moderate-to-vigorous physical

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Sitting time and mortality from all causes, cardiovascular disease, and cancer.

OBJECTIVE —Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk.

RESEARCH DESIGN AND METHODS —Participants ( n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004–2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute−1 < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min ≥100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis.

RESULTS —Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized β = −0.16, 95% CI −0.31 to −0.02, P = 0.026), BMI (β = −0.19, −0.35 to −0.02, P = 0.026), triglycerides (β = −0.18, −0.34 to −0.02, P = 0.029), and 2-h plasma glucose (β = −0.18, −0.34 to −0.02, P = 0.025).

CONCLUSIONS —This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.

https://care.diabetesjournals.org/content/diacare/31/4/661.full.pdf

Breaks in Sedentary Time: Beneficial associations with metabolic risk

Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises.

Diabetes mellitus in the pima indians: Incidence, risk factors and pathogenesis

Impaired glucose tolerance is a well documented consequence of absolute bedrest in man. Previous studies have shown a decrease in forearm glucose uptake during intravenous glucose infusion after fourteen days of bedrest. Bedrest is associated not only with physical inactivity but with a change in gravitational vector. This study was designed to examine the individual contributions of these factors to the glucose intolerance of bedrest. Thus, glucose tolerance tests were carried out in exercising subjects at bedrest and in rhesus monkeys immobilized in the vertical plane. Exercise in man improved glucose tolerance during bedrest, and vertically immobilized monkeys demonstrated significant glucose intolerance. It is concluded that the glucose intolerance of bedrest is a function of the decrease in physical activity.

Glucose Intolerance During Decreased Physical Activity in Man

Impairment of peripheral glucose utilization in normal subjects by prolonged bed rest.

TWO CASES of retroperitoneal fibrosis were described by Ormond in 1948, 1 and since then more than 125 cases have been reported. The classical description of the disease includes symptoms of anorexia, fatigue, backache, and flank pain with progressive oliguria and azotemia. Pathologically, the triad of hydronephrosis, medial ureteral deviation, and external ureteral compression by a mass of fibrous tissue has been prominent. Suggestions as to the etiology of the entity have ranged from a neoplastic process, an organized retroperitoneal hematoma, a primary urinary infection, and more recently to a primary vasculitis and hypersensitivity reaction. 2-5 However, case reports demonstrating an association between idiopathic retroperitoneal fibrosis and other collagen diseases are sparse. Although it is probable that the disorder should not be considered of a unitarian origin, the present report describes a patient with idiopathic retroperitoneal fibrosis developing in the course of an illness suggestive of systemic lupus erythematosus. It

Idiopathic retroperitoneal fibrosis and probable systemic lupus erythematosus.

The role of the liver in the total metabolic clearance of growth hormone from plasma in man was evaluated using HGH 131I and the constant infusion to equilibrium technique. Five normal subjects and four patients with cirrhosis and portal hypertension were studied after an overnight fast. HGH 131I was infused into an antecubital vein and blood samples were obtained at equilibrium from a brachial artery and hepatic vein and assayed for immunoprecipitable HGH 131I. Hepatic plasma flow was determined using in-docyanine green by the Fick calculations. The mean metabolic clearance rate (MCR) for the normal subjects was 147 ± 22 ml/min; the mean hepatic clearance of GH (CH) was 139 ± 13 ml/min. The CH represented 95 ± 6% of the total MCR. The mean hepatic plasma flow of the patients with cirrhosis was reduced when compared to the normal group, 880 ± 131 vs. 1037 ± 91 ml/min, p < 0.05. The cirrhotic patients MCR, 169 ± 27 ml/min, CH 124 ± 20 ml/min, and CH percent of MCR 76 ± 21 did not differ from the normal gro...

Hepatic clearance of human growth hormone.

Intravenous and oral glucose tolerance tests were done and EEG were monitored on healthy subjects following nights of normal sleep, following nights during which deep sleep and concomitant GH release were delayed until early in the morning, and following nights in which deep sleep and GH elevation were deprived. Glucose tolerance tests were also done at 1:00 am while awake and while sleeping, 90 min following the GH-release deep sleep period. Glucose tolerance was unchanged following the night of deep sleep deprivation, during which time no GH peaks were found. However, following deep sleep during which GH release occurred, significant glucose intolerance was seen. Glucose intolerance was demonstrated both in the sleeping subject at 1:00 am and in the awake subject on the morning following deep sleep and concomitant GH release delay. Serum immunoreactive insulin concentrations during the glucose tolerance tests following GH release were unchanged as compared to control. Sustained hyperglycemia pr...

Richard L. Lipman

Papers

Glucose Intolerance During Decreased Physical Activity in Man

Impairment of peripheral glucose utilization in normal subjects by prolonged bed rest.

Idiopathic retroperitoneal fibrosis and probable systemic lupus erythematosus.

Hepatic clearance of human growth hormone.

Growth hormone secretion during sleep: impairment in glucose tolerance and nonsuppressibility by hyperglycemia.