Effects of Moderate Weight Loss and Orlistat on Insulin Resistance, Regional Adiposity, and Fatty Acids in Type 2 Diabetes

Kelley, David E.; Kuller, Lewis H.; McKolanis, Therese M.; Harper, Patricia H.; Mancino, Juliet; Kalhan, Satish C.

doi:10.2337/diacare.27.1.33

Cited by 141 publications

(131 citation statements)

References 45 publications

(44 reference statements)

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“…Details of this trial, including results of intervention at 6 months, have been published (23). Briefly, this was a singlecenter, randomized, double-blinded, placebo-controlled, clinical trial of a behavioral weight loss intervention combined with orlistat (IntϩO group) or placebo (IntϩP group) in overweight and obese patients with type 2 diabetes.…”

Section: Research Design and Methods -mentioning

confidence: 99%

Effect of Weight Loss and Nutritional Intervention on Arterial Stiffness in Type 2 Diabetes

Barinas‐Mitchell

Kuller²,

Sutton-Tyrrell³

et al. 2006

Diabetes Care

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OBJECTIVE -There is increased stiffness of the large central arteries in type 2 diabetic patients, and obesity is a risk factor. However, the effect of intentional weight loss on arterial stiffness is uncertain, and the purpose of the current study was to assess this effect.RESEARCH DESIGN AND METHODS -Arterial stiffness was assessed by measuring aortic pulse wave velocity (aPWV) at baseline and at completion of a 1-year weight loss intervention. Metabolic control of type 2 diabetes was also appraised.RESULTS -Mean weight loss at 1 year in 38 volunteers with type 2 diabetes was 7.8%. There were improvements in HbA 1c , LDL cholesterol, homeostasis model assessment of insulin resistance, and inflammatory markers (plasminogen activator inhibitor-1, tumor necrosis factor-␣, interleukin-6, and C-reactive protein). There was also a significant improvement in aPWV at completion of weight loss intervention, from 740 to 690 cm/s (P Ͻ 0.05).CONCLUSIONS -Moderate weight loss improves arterial stiffness in type 2 diabetes.

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Section: Research Design and Methods -mentioning

confidence: 99%

Effect of Weight Loss and Nutritional Intervention on Arterial Stiffness in Type 2 Diabetes

Barinas‐Mitchell

Kuller²,

Sutton-Tyrrell³

et al. 2006

Diabetes Care

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“…Studies with tetrahydrolipstatin (Orlistat), a lipase inhibitor that causes fat malabsorption in humans, improved postprandial serum lipid profi les and insulin sensitivity and reduced risk for developing type-2 diabetes ( 20,21 ). A similar effect would be expected if Cys92 colipase leads to fat malabsorption.…”

Section: Discussionmentioning

confidence: 99%

The Arg92Cys colipase polymorphism impairs function and secretion by increasing protein misfolding

Xiao

Ferguson

Magee

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org many constituents present in intestinal lumen, including bile salts, phospholipids, cholesterol esters, dietary proteins, and carbohydrates, inhibit PTL, another pancreatic protein, colipase, is required for PTL activity ( 2 ).Hence, colipase plays an important role in dietary fat digestion. Colipase is predominantly expressed in the exocrine pancreas and, to a lesser degree, in the stomach and intestine. Newly synthesized colipase contains a 17 amino acid signal peptide and a 5 amino acid propiece at the N-terminus. The propiece is cleaved from procolipase to form colipase and releases a pentapeptide named enterostatin ( 3 ). Enterostatin is a satiety factor that reduces voluntary fat intake in animals ( 4 ). Mature colipase is a 10 kDa protein with minimal secondary structure. Five disulfi de bonds determine the folding of colipase and stabilize the loops or fi ngers of colipase ( 5 ) ( Fig. 1 ). The limited secondary structure protects colipase from surface denaturation and accounts for its high stability in adverse environments ( 5 ). Models of colipase function include a lipid-binding surface on the tips of the loops and a PTLbinding surface on the opposite surface. Colipase anchors PTL on the emulsion surface and stabilizes the active conformation of PTL ( 6 ).Analysis of genomic sequence data identifi ed a polymorphism in codon 109 of human colipase gene, resulting in an arginine-to-cysteine substitution at position 92 (Arg92Cys) of procolipase. Several studies have reported that the Arg92Cys substitution in colipase increased the odds risk for developing type-2 diabetes in two independent Caucasian populations ( 7, 8 ). The authors speculated that the polymorphism contributes to increased susceptibility for type-2 diabetes by infl uencing postprandial serum triglyceride levels or by altering lipoprotein metabolism. No direct evidence supports either of these hypotheses. In Western diets, triglycerides constitute 95% of dietary fats and provide 30-40% of total caloric intake. Prior to absorption, triglycerides must be hydrolyzed to free fatty acids or monoglycerides by the concerted action of lipases ( 1 ). The majority of fatty acids are released in the duodenum by pancreatic triglyceride lipase (PTL Abbreviations: Arg92, arginine 92; Arg92Cys, arginine-to-cysteine substitution at position 92; Cys92, cysteine 92; ER, endoplasmic reticulum; NaTDC, sodium taurodeoxycholate; PDI, protein disulfi de isomerase; PTL, pancreatic triglyceride lipase; UPR, unfolded protein response; Xbp1, X-box binding protein-1.

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“…Влияние орлистата на улучшение чувствительности к инсулину, не зависящее от снижения массы тела, было показано в рандомизированном исследовании эффек-тов монотерапии орлистата у больных сахарным диабе-том 2 типа [15]. У наших пациенток обеих возрастных групп при приеме орлистата также отмечалась нормали-зация уровней тощакового и стимулированного инсу-лина, индекса HOMA-IR.…”

Section: результаты исследования и их обсуждениеunclassified

Narusheniya menstrual'nogo tsikla u podrostkovi molodykh zhenshchin s ozhireniem

Кузнецова¹,

Mikhaelyants²,

Santa-Mariya-Fernandes³

et al. 2010

Obes. metabol.

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Obesity plays a key role in reproductive disorders. Xenical administration results in recovery of menstrual function in 78.9% and ovulation in 26.3% of patients with obesity. Hormone therapy in patients with obesity should be accompanied with Xenical therapy, which has a favorable impact on further body weight reduction (13.95% from baseline) and improvement (or stability) of metabolic parameters.

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Effects of Moderate Weight Loss and Orlistat on Insulin Resistance, Regional Adiposity, and Fatty Acids in Type 2 Diabetes

Cited by 141 publications

References 45 publications

Effect of Weight Loss and Nutritional Intervention on Arterial Stiffness in Type 2 Diabetes

Effect of Weight Loss and Nutritional Intervention on Arterial Stiffness in Type 2 Diabetes

The Arg92Cys colipase polymorphism impairs function and secretion by increasing protein misfolding

Narusheniya menstrual'nogo tsikla u podrostkovi molodykh zhenshchin s ozhireniem

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