Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.

The Effects of Water-based Exercise Training in People with Type 2 Diabetes.

PURPOSE: To investigate the effects of 8 wk of upright water-based exercise training in people with type 2 diabetes. METHODS: Thirteen participants with type 2 diabetes (54% male; 60.9 ± 9.6 yr, mean ± standard deviation) completed 8 wk of upright water-based exercise training at a moderate intensity (60%-80% of exercise test-derived maximum HR), for 1 h, three times a week (TG). Fourteen participants (64% male; 63.9 ± 9.8 yr) acted as a control group (CG) who maintained their usual activities. Preintervention and postintervention, participants performed cardiopulmonary exercise testing to determine V˙O2peak and one-repetition maximum testing to assess muscular strength. Blood profiles were assessed with standard assays. Body mass index and waist/hip ratio were employed as measures of anthropometry. Endothelium-dependent (brachial artery flow-mediated dilation) and independent (glyceryl trinitrate-mediated) function were assessed using vascular ultrasound. RESULTS: Water-based training increased V˙O2peak (18.5 ± 4.3 mL·kg·min to 21.5 ± 5.4 mL·kg·min) (P = 0.002), overall muscle strength (123 ± 44 kg to 139 ± 43 kg) and leg strength (92 ± 28 kg to 104 ± 29 kg), compared with the CG (P = 0.001). The effect on pectoral strength (31 ± 17 kg to 35 ± 16 kg) was not significantly different to the CG (24 ± 12 kg to 26 ± 14 kg) (P = 0.08). No change was observed in anthropometry, blood profiles, or glyceryl trinitrate-mediated vascular function. Flow-mediated dilation was increased after training (6.1% ± 2.4% to 6.5% ± 3.0%), compared with controls who demonstrated a slight decrease (6.2% ± 1.6% to 5.4% ± 1.6%) (P = 0.002). CONCLUSIONS: Water-based circuit training was well tolerated and appears to be an effective exercise modality for improving aerobic fitness, strength, and vascular function in people with type 2 diabetes.

Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis.

Renal tubular acidosis is an underreported complication of ibuprofen misuse, and can result in life-threatening hypokalaemia. We describe four patients who presented with profound hypokalaemia and muscle weakness associated with excessive ibuprofen ingestion. Ibuprofen cessation and supportive management resulted in complete biochemical resolution within a few days. These cases remind practitioners about potential complications of unmonitored use of over-the-counter analgesics, including those with potential for misuse due to their codeine content.

Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection.

Treated HIV infection and HIV-lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection.