Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.

BACKGROUND: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. OBJECTIVE: We aimed to examine the direct and/or indirect role of GH on TRL metabolism. METHODS: We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. RESULTS: After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. CONCLUSION: In this relatively short term 'loss of function' human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.

Concomitant Peripheral Neuropathy and Type 2 Diabetes Impairs Postexercise Cutaneous Perfusion and Flowmotion.

CONTEXT: Type 2 diabetes and peripheral neuropathy exhibit microvascular dysfunction at rest. However, data regarding their microvascular perfusion during exercise remain scarce. OBJECTIVE: This study investigated changes in microvascular perfusion during postexercise recovery in those with type 2 diabetes, with or without peripheral neuropathy, as well as in healthy controls and those with obesity. METHODS: Skin blood perfusion was assessed in each group using laser Doppler flowmetry (LDF) and laser speckle contrast imaging before and immediately after a 6-minute walking test. LDF recordings underwent wavelet transformation to allow specific control mechanisms of blood perfusion to be studied (eg, endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory, and cardiac mechanisms). RESULTS: Skin blood perfusion increased after exercise in all groups (22.3 ±â€…28.1% with laser speckle contrast imaging and 22.1 ±â€…52.5% with LDF). Throughout postexercise recovery, the decrease was blunted in those with subclinical peripheral neuropathy and confirmed peripheral neuropathy when compared to the other 3 groups. After exercise, total spectral power increased in all groups. The relative contributions of each endothelial band was lower in those with confirmed peripheral neuropathy than in the healthy controls and those with obesity (nitric oxide-dependent function: 23.6 ±â€…8.9% vs 35.5 ±â€…5.8% and 29.3 ±â€…8.8%, respectively; nitric oxide-independent function: 49.1 ±â€…23.7% vs 53.3 ±â€…10.4% and 64.6 ±â€…11.4%, respectively). The neurogenic contribution decreased less in those with confirmed peripheral neuropathy and in those with type 2 diabetes alone, compared to those with subclinical peripheral neuropathy and those with obesity (-14.5 ±â€…9.9% and -12.2 ±â€…6.1% vs -26.5 ±â€…4.7% and -21.7 ±â€…9.4%, respectively). CONCLUSION: Peripheral neuropathy, whatever the stage, altered the microvascular response to exercise via impaired endothelial and neurogenic mechanisms.

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial.

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: -1.44% and G3: -1.48% vs. G1: -0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.

Effects of exercise training on arterial function in type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Controversy exists among trials assessing whether exercise can improve arterial function in type 2 diabetes mellitus (T2DM) subjects. Therefore the aim of this study was to systematically review and quantify the effects of exercise on arterial function in T2DM subjects. METHODS: MEDLINE, Cochrane, Scopus and Web of Science were searched up until January 2013 for randomized controlled trials evaluating the effects of exercise interventions lasting 4 weeks or more on arterial function in T2DM subjects. Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial conduit artery were considered for assessment of arterial endothelial function and smooth muscle function, respectively. RESULTS: Five randomized trials comparing exercise and control groups (overall n = 217) met the inclusion criteria. The mean exercise characteristics were as follows: 3.6 sessions per week, 67.5 min per session, intensity at 74.4 % of the maximum heart rate (HR(max)), for 14 weeks. The post-intervention mean difference in FMD favoured the exercise groups over the control groups (2.23 %; P < 0.0001). No significant post-intervention mean difference in NMD (1.22 %; P = 0.29) was found between the groups. Neither heterogeneity nor publication bias was detected among the trials. CONCLUSION: Exercise training alone improved FMD, showing its capacity to restore arterial endothelial function in T2DM subjects. However, further research is needed to determine whether longer and/or more intense exercise interventions could enhance arterial smooth muscle function in this population.