Use of a reference four-component model to define the effects of insulin treatment on body composition in type 2 diabetes: the ?Darwin study?

Packianathan, I; Fuller, N. J.; Peterson, David B.; Wright, Antony; Coward, W. A.; Finer, Nick

doi:10.1007/s00125-004-1642-x

Cited by 28 publications

(31 citation statements)

References 35 publications

(57 reference statements)

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“…Higher MS in type 1 diabetic patients versus T2D has been reported by Cetinus et al, as compared to age-matched control subjects [21]. The correlation between the decrease in HbA1c and BW gain, and with insulin doses have been reported by other authors [18, 20]. …”

Section: Discussionmentioning

confidence: 62%

“…Overall our results are in agreement with previous studies. In T2D, previous studies reported that BW gain (+1.6 ± 4.9 to +5.2 ± 2.7 kg at six months) was mainly composed of fat [15–20]. We confirm the predominance of FM gain in insulin-treated T2D as it represented the entire BW gain; we demonstrated for the first time the absence improvement in MS after insulin therapy in type2 diabetic patients that confirm the absence of improvement in FFM during weight gain in insulin treated T2D.…”

Section: Discussionmentioning

confidence: 99%

“…However, the excess fat is deposited essentially in the intra-abdominal area [20]. Although we did not use DEXA to determine the distribution of FM gain, we observed an increase in WC, which is a good indicator of visceral FM [27].…”

Section: Discussionmentioning

confidence: 99%

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Insulin Therapy and Body Weight, Body Composition and Muscular Strength in Patients with Type 2 Diabetes Mellitus

Gin

Rigalleau

Perlemoine

2010

Journal of Nutrition and Metabolism

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Aims. To determine the progression of body weight (BW) and body composition (BC) in patients with type 2 diabetes mellitus (T2D) on insulin therapy and the consequences on muscle strength (MS) as a reflect of free fat mass increases. Research design and methods. We analysed BC using air displacement plethysmography and MS by hand grip dynamometry in 40 T2D before and after three (M3) and six months (M6) of insulin therapy. Results. at baseline HbA1c was 9.76 ±1.6% and BW was stable with fat mass (FM) 28 ± 10.7 kg; and fat free mass (FFM) 52.4 ± 11 kg; at M6, HbA1c improved to 7.56 ± 0.8%; insulin doses tended to increase. BW gain at M6 was + 3.2 ± 4.2 kg and with an increase of only 25% by M3; it was composed of FM, whereas FFM was unchanged. MS did not increase on insulin therapy. Conclusions. In T2D, BW gain was composed exclusively of FM with no improvement in MS.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Insulin Therapy and Body Weight, Body Composition and Muscular Strength in Patients with Type 2 Diabetes Mellitus

Gin

Rigalleau

Perlemoine

2010

Journal of Nutrition and Metabolism

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“…However, insulin therapy is associated with weight gain [11,12], predominantly fat mass [13], which increases insulin resistance and necessitates the use of higher doses of insulin at the expense of further weight gain. The exact role of insulin in human skeletal muscle metabolism, however, continues to raise debate.…”

Section: Introductionmentioning

confidence: 99%

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

et al. 2015

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Aims/hypothesis We aimed to investigate the role of insulin in regulating human skeletal muscle metabolism in health and diabetes. Methods We conducted a systematic review and metaanalysis of published data that examined changes in skeletal muscle protein synthesis (MPS) and/or muscle protein breakdown (MPB) in response to insulin infusion. Random-effects models were used to calculate weighted mean differences (WMDs), 95% CIs and corresponding p values. Both MPS and MPB are reported in units of nmol (100 ml leg vol.)Results A total of 104 articles were examined in detail. Of these, 44 and 25 studies (including a total of 173 individuals) were included in the systematic review and meta-analysis, respectively. In the overall estimate, insulin did not affect MPS 8.55], p=0.71), but significantly reduced MPB .18], p<0.001). Overall, insulin significantly increased net balance protein acquisition (WMD 20.09 [95% CI 15.93,24.26], p<0.001). Subgroup analysis of the effect of insulin on MPS according to amino acid (AA) delivery was performed using meta-regression analysis. The estimate size (WMD) was significantly different between subgroups based on AA availability (p=0.001). An increase in MPS was observed when AA availability increased (WMD 13.44 [95% CI 4.07,22.81], p<0.01), but not when AA availability was reduced or unchanged. In individuals with diabetes and in the presence of maintained delivery of AA, there was a significant reduction in MPS in response to insulin (WMD −6.67 [95% CI −12.29, −0.66], p<0.05). Conclusions/interpretation This study demonstrates the complex role of insulin in regulating skeletal muscle metabolism. Insulin appears to have a permissive role in MPS in the presence of elevated AAs, and plays a clear role in reducing MPB independent of AA availability.

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“…Waist and hip circumferences were measured according to a standardized protocol (15). Body weight and fat mass were assessed using the Tanita bioimpedance balance (Yiewsley, UK) (26).…”

Section: Oral Glucose Tolerance Testmentioning

confidence: 99%

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

Anderwald-Stadler¹,

Krebs²,

Promintzer³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n ϭ 18, 13 females and 5 males, age 47 Ϯ 2 yr, BMI ϭ 25.5 Ϯ 0.9 kg/m 2 ) and low (IR; n ϭ 18, 12 females and 6 males, age 45 Ϯ 2 yr, P ϭ 0.49, BMI ϭ 27.5 Ϯ 1.1 kg/m 2 , P ϭ 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU ⅐ min Ϫ1 ⅐ m Ϫ2 ) isoglycemic clamp tests. M100-120 min was higher in IS (10.7 Ϯ 0.7) than in IR (4.4 Ϯ 0.2 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 , P Ͻ 10 Ϫ9 ), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 Ϯ 6% vs. IS: 82 Ϯ 5%, P Ͻ 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24 -28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 Ϯ 26 pg/ml vs. IS: 469 Ϯ 23 pg/ml, P Ͻ 0.02). Clamp insulin infusion reduced plasma obestatin to ϳ81% of basal values in IS (P Ͻ 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M (r ϭ 0.34, P ϭ 0.04), HDL cholesterol (r ϭ 0.45, P ϭ 0.01), and plasma ghrelin concentrations (r ϭ 0.80, P Ͻ 0.000001) and negatively with measures of adiposity, plasma FFA during clamp (r ϭ Ϫ0.42, P Ͻ 0.01), and systolic blood pressure (r ϭ Ϫ0.33, P Ͻ 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulinresistant persons.ghrelin; hyperinsulinemic clamp test; free fatty acids; appetite regulation OBESTATIN, A RECENTLY DISCOVERED 23-amino acid peptide hormone, is derived by posttranslational cleavage of the same peptide precursor (preproghrelin) as ghrelin, which is a 28-amino acid peptide released from the stomach (34, 38). Obestatin appears to have actions opposite to ghrelin in the regulation of food intake, emptying of the stomach, and body weight in rodents and could be part of a dual system connecting the gut and the brain to regulate energy homeostasis (38). However, other recent studies (25, 32, 36) did not provide evidence for a crucial role of obestatin in regulating food intake. Intracerebroventricular and intravenous administration of obestatin in rats did not affect food intake and could not antagonize the ghrelin-stimulated increase in food intake.The administration of ghrelin increased the food intake and body weight in rodents and humans (23,34, 35) and accelerated gastric emptying (10). In the presence of a negative energy balance, such as starvation, cachexia, or anorexia nervosa, the secretion of ghrelin increa...

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Use of a reference four-component model to define the effects of insulin treatment on body composition in type 2 diabetes: the ?Darwin study?

Cited by 28 publications

References 35 publications

Insulin Therapy and Body Weight, Body Composition and Muscular Strength in Patients with Type 2 Diabetes Mellitus

Insulin Therapy and Body Weight, Body Composition and Muscular Strength in Patients with Type 2 Diabetes Mellitus

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

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