Effects of growth hormone administration in human obesity

OBJECTIVE: To summarize the reports in the literature regarding the effect of growth hormone (GH) treatment of obesity. RESEARCH METHODS AND PROCEDURES: Clinical trials of GH treatment of obese adults were reviewed and summarized. Specifically, information regarding the effects of GH on body fat and body fat distribution, glucose tolerance/insulin resistance, and adverse consequences of treatment were recorded. RESULTS: GH administered together with hypocaloric diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity. In all but one study, glucose tolerance during GH treatment suffered relative to placebo. CONCLUSION: The bulk of studies indicate little or no beneficial effects of GH treatment of obesity despite the low serum GH concentrations associated with obesity.     

A blood fluidizing activity

The viscosity, hematocrit and plasma proteins, determined by simple techniques on one ml of blood, were some of the parameters observed in a long term study of clinical thromboembolism. The known dependence of viscosity on the hematocrit and plasma proteins was usually observed, but frequent exceptions were found. Many viscosities appeared that were far less than expected from the blood's composition. These variations were attributed to a blood fluidizing activity that was not dependent on dilution. This activity was quantized by a formula that expressed it in percent. Its normal range of activity was delineated by analysis of 1000 tests on 200 well individuals, and its general behavior outlined by 5239 tests on a variety of patients seen in practice. Extended follow-up studies on many normal subjects and patients indicated that the intensity of fluidizing activity was characteristic for the individual, and seemed to be directed by a mechanism whose control settings may vary. It was suggested that this fluidizing activity may play a prominent role in blood rheology.     

Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity.

BACKGROUND & AIMS: The aim of our study is to report our observations on the change in liver function tests of volunteers receiving pioglitazone as part of a study of its effects on fatty acid metabolism. Treatment with other thiazolidinediones has been reported to ameliorate non-alcoholic fatty liver disease (NAFLD) in obese and diabetic humans, but whether pioglitazone has similar effects has not been reported. METHODS: Five of 20 upper body obese volunteers (10 men, 10 premenopausal women) had abnormal baseline liver enzymes (3 had ultrasonographic evidence of hepatic steatosis). All volunteers were treated with 30 mg pioglitazone per day for 18 +/- 0.4 weeks. Body composition, blood lipids, and insulin sensitivity (intravenous glucose tolerance test) were assessed at baseline and after pioglitazone treatment. RESULTS: During pioglitazone treatment, the liver enzyme abnormalities uniformly improved in subjects with evidence of NAFLD, primarily during the first 2 months. Some parameters of insulin sensitivity improved when measured after 18 weeks of pioglitazone treatment. Liver function tests remained normal in the 15 volunteers without evidence of NAFLD. CONCLUSIONS: Liver function studies improved in obese volunteers with NAFLD during pioglitazone treatment. Although the nature of our observations does not prove a cause and effect relationship between pioglitazone treatment and improvement in liver enzymes, the time course and magnitude of improvement we observed may facilitate future research into thiazolidinedione treatment of NAFLD.     

Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study

BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.     

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review

Rigorous glycaemic control—reflected by low HbA1c goals—is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short‐term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross‐sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring‐derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN.     

Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers

BACKGROUND: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. CONCLUSION: Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.     

Superficial thrombophlebitis of the venous dorsal arch of the foot and deep venous thrombosis after foam sclerotherapy

Four days after foamsclerotherapy of an incompetent great saphenous vein of the left lower leg a 49-year-old woman developed a superficial thrombophlebitis of the venous dorsal arch. In the course of follow-up repeated color duplex sonography initially did not show involvement of the deep venous system and, hence, she was treated with non-steroidal anti-inflammatory drugs and compression hosiery. However, six weeks after foam treatment we diagnosed a deep venous thrombosis (DVT) of the popliteal vein and started an oral anticoagulant therapy. Although rarely observed, DVT is among the most serious complications of foamsclerotherapy Therefore, we suggest that the occurrence of a superficial thrombophlebitis that is not located in close vicinity of the vein treated should be an indication for regular follow-up examinations to prevent missing the occurrence of disease progression and a possible involvement of the deep venous system.