Increased Fat Mass Compensates for Insulin Resistance in Abdominal Obesity and Type 2 Diabetes

Virtanen, Kirsi A.; Iozzo, Patricia; Hällsten, Kirsti; Huupponen, Risto; Parkkola, Riitta; Janatuinen, Tuula; Lönnqvist, Fredrik; Viljanen, Tapio; Rönnemaa, Tapani; Lönnroth, Peter; Knuuti, Juhani; Ferrannini, Ele; Nuutila, Pirjo

doi:10.2337/diabetes.54.9.2720

Cited by 104 publications

(89 citation statements)

References 36 publications

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“…To our knowledge, there are relatively few studies that have explored the use of dynamic [ 18 F]-FDG PET to quantitatively analyze tissue-specific GU in VF and SC fat (10,30) and skeletal muscle (31). Based on the current data, obese T2D have decreased GU in skeletal muscles compared with ND and control subjects; this confirms previous results by our group (31).…”

Section: Discussionsupporting

confidence: 81%

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Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

et al. 2015

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OBJECTIVEWe investigated fat distribution and tissue-specific insulin-stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. RESEARCH DESIGN AND METHODSA total of 23 obese patients (BMI 43.0 6 3.6 kg/m 2 ; 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [18 F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. RESULTSAt baseline, visceral fat GU was 30 6 7% of muscle GU in control subjects and 57 6 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (∼40%) more than subcutaneous fat (7%). Tissue-specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. CONCLUSIONSBariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose.Visceral fat (VF) and subcutaneous fat (SC) are structurally, metabolically, and functionally distinct, albeit both contribute to obesity (1). Abdominal SC fat has clearly defined, metabolically distinct deep and superficial layers separated by the Scarpa fascia (2,3). Research suggests that the deep layers are metabolically more active

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Section: Discussionsupporting

confidence: 81%

“…Based on the current data, obese T2D have decreased GU in skeletal muscles compared with ND and control subjects; this confirms previous results by our group (31). The decreased skeletal muscle GU in T2D in response to insulin may be due, at least in part, to increased FFA levels (32), i.e., a model of substrate competition.…”

Section: Discussionsupporting

confidence: 80%

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

et al. 2015

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“…The values and variations of M or M/I seen in this experiment are comparable to published values for healthy subjects 23,24,26,27 and obese and non-obese subjects with and without type 2 diabetes. 28 The only other study on CLA isomer mixture using the euglycemic hyperinsulinemic clamp technique reported M to be 3.7-4.5 mg min À1 bw À1 (range of means) in obese men with the metabolic syndrome, 18 which is lower than M values of 5.1-6.2 mg min À1 bw À1 observed in the present study comprising male and female subjects. In our study, healthy overweight and obese subjects had a median M/I of 7.6-8.2 M mU À1 l (corrected for bw), which is similar to type 2 diabetics with mean BMI of 23.1 kg/m 2 but without the metabolic syndrome.…”

Section: Discussioncontrasting

confidence: 74%

“…The importance of abdominal fat mass for insulin resistance is well established. Indeed, Virtanen et al 28 have shown that mild, recent diabetes, adds little to the insulin resistance compared to abdominal obesity. However, we were unable to correlate individual changes in either lbm, total fat mass or trunk fat mass, which in some cases were quite large (e.g.…”

Section: Discussionmentioning

confidence: 99%

The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese

Syvertsen¹,

Halse²,

Ho³

et al. 2006

Int J Obes

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Background: Contradicting results have been published regarding the effect of conjugated linoleic acid (CLA) on insulin resistance. However, only a few studies have used the euglycemic hyperinsulinemic clamp method, which is considered the standard for measuring insulin resistance. Objective: To evaluate if CLA as a mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the insulin resistance in healthy overweight and obese male and female adults. Design: The main study was a randomized, double-blind, placebo-controlled trial with change in body composition as primary end point comprising 118 subjects receiving supplementation with either placebo (olive oil) or CLA (Clarinol) for 6 months. A sub-population of 49 subjects agreed additionally to participate in an euglycemic hyperinsulinemic clamp study at baseline and after 6 months of supplementation with study drug. The primary outcome was the change in glucose uptake (M) as measured by the hyperinsulinemic euglycemic glucose clamp method. Secondary outcomes were the correlates between insulin resistance and changes in body composition or blood chemistry parameters. Forty-one subjects completed the clamp test at both time points. Results: The median M of the CLA group was 11.0 mg min À1 lean body mass (lbm) À1 (n ¼ 24) at baseline, 10.3 mg min À1 lbm À1 (n ¼ 24) after 6 months, and the median difference was þ 0.21 mg min À1 lbm À1 (n ¼ 24). The median M of placebo group was 8.4 mg min À1 lbm À1 at baseline and 9.3 mg min À1 lbm À1 after 6 months and the median difference was À0.22 mg min À1 lbm À1 (n ¼ 17). No significant (Po0.05) differences were found within groups or between groups. Likewise, the glucose uptake insulin concentration ratio during clamp (M/I) was independent of treatment and time. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index derived from fasting glucose and insulin were also independent of treatment and time, and HOMA for the clamp population (n ¼ 49) corresponded well with HOMA for the per protocol population (n ¼ 83). Correlation analysis showed that changes in M were inversely correlated to changes in glucohemoglobin (P ¼ 0.002), but did not correlate with changes in either glucose, insulin, insulin c-peptide, leptin, adiponectin or percent body fat. Conclusions: CLA does not affect glucose metabolism or insulin sensitivity in a population of overweight or obese volunteers.

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“…Although majority of glucose metabolism irregularities associated with SGAs therapy are secondary to weight gain (Newcomer, 2005), that causality could run in the opposite direction (Figure 4). That is to say, in addition to decreasing the ability of homeostatic and reward regions sensing of adiposity-or food-related signals (Figure 5b; Figlewicz, 2003aFiglewicz, , b, 2004Berthoud, 2004b), insulin resistance increases body fat mass as it tends not to afflict adipose tissue that retains insulin sensitivity even in the face of other tissues' resistance (Mizuno et al, 2004;Virtanen et al, 2005;Isganaitis and Lustig, 2005).…”

Section: Putative Mechanisms Of Sgas-induced Weight Gainmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Increased Fat Mass Compensates for Insulin Resistance in Abdominal Obesity and Type 2 Diabetes

Cited by 104 publications

References 36 publications

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

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