1.
Current treatment options for nonalcoholic fatty liver disease.
Shetty, A, Syn, WK
Current opinion in gastroenterology. 2019;(3):168-176
Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the United States and is strongly associated to the metabolic syndrome. In this review, we will discuss the evidence behind the current recommendations on lifestyle modifications and available treatment options for NAFLD. RECENT FINDINGS The unrelenting rise in obesity and diabetes epidemic has led to a large healthcare burden from NAFLD and it is projected to continue to grow over the next two decades. Lifestyle modification that leads to weight loss is effective at treating NAFLD, but these modifications require a multidisciplinary approach for success in the real world. Multiple pharmacologic treatment options have been studied with promising results, but none have been approved for treatment in the United States. Clinical trials are on-going to study further pharmacologic treatment alternatives. SUMMARY NAFLD is the most common chronic liver disease in United States, and an independent risk factor for mortality. Implementation of lifestyle modifications through a multidisciplinary approach and careful selection of patients for pharmacologic interventions will be essential for successful management of NAFLD.
2.
Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome.
Straznicky, NE, Grima, MT, Sari, CI, Eikelis, N, Lambert, GW, Nestel, PJ, Richards, K, Dixon, JB, Schlaich, MP, Lambert, EA
Metabolism: clinical and experimental. 2015;(7):797-803
Abstract
CONTEXT Insulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis. OBJECTIVE This study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome. METHODS Un-medicated individuals (n=42, mean age 56±0.8 yrs, body mass index 34±0.6 kg/m(2)) were randomised to 12-weeks pioglitazone (PIO, 15 mg for 6 weeks, then 30 mg daily) or placebo using a double-blind, parallel group design. Whole-body norepinephrine kinetics (arterial norepinephrine concentration, calculated spillover and clearance rates), spontaneous cardiac baroreflex sensitivity, heart rate and blood pressure were measured at times 0, 30, 60, 90 and 120 minutes during OGTT. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M) and Matsuda index. RESULTS PIO increased clamp derived glucose utilisation by 35% (P<0.001) and there were concurrent reductions in inflammatory status and plasma triglycerides (P<0.05). Fasting norepinephrine kinetic parameters were unaltered. PIO treatment was associated with lower plasma insulin incursions, greater reduction in diastolic blood pressure and enhanced baroreflex sensitivity during OGTT (P all <0.05). The overall norepinephrine spillover response (AUC(0-120)) increased significantly in the PIO group (group × time interaction, P=0.04), with greatest increment at 30 minutes post-glucose (101±38 ng/min at baseline versus 241±48 ng/min post treatment, P=0.04) and correlated with percent improvement in M. CONCLUSIONS PIO enhances the early postprandial SNS response to carbohydrate ingestion.
3.
A randomized controlled trial of the effects of pioglitazone treatment on sympathetic nervous system activity and cardiovascular function in obese subjects with metabolic syndrome.
Straznicky, NE, Grima, MT, Sari, CI, Eikelis, N, Lambert, GW, Nestel, PJ, Karapanagiotidis, S, Wong, C, Richards, K, Marusic, P, et al
The Journal of clinical endocrinology and metabolism. 2014;(9):E1701-7
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Abstract
CONTEXT Insulin resistance and sympathetic nervous system overactivity are closely associated and contribute to cardiovascular risk. OBJECTIVE The objective of the study was to test the hypotheses that pharmacological improvement in insulin sensitivity would (1) attenuate sympathetic neural drive and (2) enhance neuronal norepinephrine uptake. PARTICIPANTS AND METHODS A randomized, double-blind trial was conducted in 42 obese, unmedicated individuals with metabolic syndrome (mean age 56 ± 1 y, body mass index 34 ± 0.6 kg/m(2)) who received 12 weeks of pioglitazone (PIO; 15 mg for 6 wk, then 30 mg daily) or matched placebo. Clinical measurements included whole-body norepinephrine kinetics [spillover rate, plasma clearance, and the steady state ratio of tritiated 3,4-dihydroxyphenylglycol to tritiated norepinephrine ([(3)H]-DHPG to [(3)H]-NE) as an index of neuronal uptake-1], muscle sympathetic nerve activity, spontaneous baroreflex sensitivity, euglycemic hyperinsulinemic clamp, oral glucose tolerance test, ambulatory blood pressure, and Doppler echocardiography. RESULTS PIO treatment increased glucose uptake by 35% and was accompanied by significant reductions in diastolic blood pressure and improved left ventricular diastolic and endothelial function. Resting muscle sympathetic nerve activity burst frequency decreased by -6 ± 3 burst/min compared with baseline (P = .03), but the magnitude of change was not different from placebo (P = .89). Norepinephrine spillover and clearance rates and baroreflex sensitivity were unchanged. Post hoc subgroup analyses revealed an 83% increase in [(3)H]-DHPG to [(3)H]-NE ratio in hyperinsulinemic (P = .04) but not normoinsulinemic subjects (time × group interaction, P = .045). Change in [(3)H]-DHPG to [(3)H]-NE ratio correlated with improvements in diastolic blood pressure (r = -0.67, P = .002), the ratio of early (E) to late (A) peak transmitral diastolic inflow velocity (r = 0.62, P = .008), E wave deceleration time (r = -0.48, P = .05), and Δinsulin area under the curve0-120 during the oral glucose tolerance test (r = -0.42, P = .08). CONCLUSIONS Compared with placebo, PIO does not affect resting sympathetic drive or norepinephrine disposition in obese subjects with metabolic syndrome. Treatment induced changes in the [(3)H]-DHPG to [(3)H]-NE ratio related to reduction in hyperinsulinemia and improvements in diastolic function.
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Treatment of polycystic ovarian syndrome with insulin resistance by insulin-sensitizer.
Hu, L, Shen, H, Wu, QF, Tian, L, Hu, MH
Clinical and experimental obstetrics & gynecology. 2014;(3):288-92
Abstract
OBJECTIVE The aim of this study was to observe clinical curative effects of combination application of dimethylbiguanide and pioglitazone and single application of pioglitazone in patients with polycystic ovarian syndrome (PCOS) complicated with insulin resistance (IR). MATERIALS AND METHODS Forty cases of patients with PCOS complicated with IR were investigated, and 20 cases of infertile women without PCOS were taken as the control group. PCOS group was divided into group A and group B according to body mass index (BMI) to detect glucose and lipids metabolism indicators, C reactive protein (CRP), etc. There were 20 cases in group A (Pioglitazone) and 20 cases in group B (dimethylbiguanide and pioglitazone). After treatment for 12 weeks, changes of the above various indicators were compared. RESULTS After treatment, insulin resistance index and serum testosterone (T) of two groups patients with PCOS significantly reduced (p < 0.05). Compared to before treatment, BMI of group B significantly reduced (p < 0.05). For INS at two hours after treatment, group B reduced more significantly (p < 0.05). CONCLUSION The combination of dimethylbiguanide and pioglitazone was more effective for the treatment of PCOS complicated with IR than simple pioglitazone; chronic inflammation occurrence was possibly one of reasons for insulin sensitivity reduction of patients with PCOS.