Insulin Sensitivity, Insulin Secretion, and Abdominal Fat

Wagenknecht, Lynne E.; Langefeld, Carl D.; Scherzinger, Ann; Norris, Jill M.; Haffner, Steven M.; Saad, Mohammed F.; Bergman, Richard N.

doi:10.2337/diabetes.52.10.2490

Cited by 276 publications

(225 citation statements)

References 44 publications

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“…Recently, we reported that fat localized in the pancreas was inversely associated with dynamic measures of b-cell function in non-diabetic men (7). Previous reports described an association of intra-abdominal fat with b-cell function (8,9); however, this was not confirmed by others (10)(11)(12). This seeming discrepancy may be due to the differences in populations studied and the methods by which b-cell function parameters were estimated.…”

Section: Introductioncontrasting

confidence: 47%

Lack of association of liver fat with model parameters of β-cell function in men with impaired glucose tolerance and type 2 diabetes

Tushuizen¹,

Bunck²,

Pouwels³

et al. 2008

European Journal of Endocrinology

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Objective: Hepatic steatosis and obesity are components of the metabolic syndrome and risk factors for developing type 2 diabetes (T2DM). We studied how liver fat and body fat distribution relate to various aspects of b-cell function. Methods: In 12 men with T2DM, 10 men with impaired glucose tolerance (IGT), and 14 age-and body mass index-matched controls, we measured body fat distribution and liver fat by magnetic resonance imaging and spectroscopy. An oral glucose tolerance test was performed to calculate insulin secretory rate (ISR) by C-peptide deconvolution, and b-cell function using a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Waist circumference and the various body fat compartments did not differ among groups. IGT had the highest total and late phase insulin secretion (P!0.001), whereas patients had the lowest insulinogenic index adjusted for insulin resistance (PZ0.006). In spite of the hypersecretion, IGT had b-cell glucose sensitivity, rate sensitivity, and potentiation similar to controls. Liver fat content was highest in diabetic patients (PZ0.004) and showed the strongest association with total and late phase of insulin secretion in the IGT group (rZ0.657, PZ0.039 and rZ0.732, PZ0.016 respectively). Model b-cell function variables showed no association with liver fat or body fat compartments. Conclusions: These data suggest that, in spite of the association of central adiposity and liver fat with T2DM risk, additional, hitherto unknown factors may contribute to b-cell dysfunction in susceptible humans.European Journal of Endocrinology 159 251-257

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Section: Introductioncontrasting

confidence: 47%

Lack of association of liver fat with model parameters of β-cell function in men with impaired glucose tolerance and type 2 diabetes

Tushuizen¹,

Bunck²,

Pouwels³

et al. 2008

European Journal of Endocrinology

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“…These relationships are likely to be due to obesity-related disturbances of glucose metabolism. Especially the visceral component of abdominal fat is strongly associated with insulin resistance [17], and thereby with a reduced ability to metabolise the glucose load of an OGTT. Interestingly, BMI in itself did not explain sex differences in 2hPG levels.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study

et al. 2010

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Aims/hypothesis We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA 1c could be explained by differences in body size and/or body composition between men and women in a general non-diabetic Danish population. Moreover, we aimed to study to what degree the newly suggested high-risk HbA 1c criteria overlapped with the current OGTT-based criteria of glucose intolerance. Methods We used cross-sectional data from 6,006 nondiabetic men and women. HbA 1c and FPG levels were measured and a 75 g OGTT was performed in all individuals. Height, weight and waist and hip circumferences were measured and BMI was calculated. Data were analysed in age-adjusted linear regression models. Results Men had higher FPG and HbA 1c levels than women, and women had higher 2hPG levels than men. Sex differences in 2hPG levels were explained by differences in height and FPG levels, but sex differences in FPG or HbA 1c levels were not explained by anthropometric measures. Among individuals with HbA 1c in the high-risk range (6.0-6.5%), 73% had normal glucose tolerance. Conclusions/interpretation Sex differences in 2hPG levels after an OGTT may to some extent be a consequence of giving the same amount of glucose to individuals with different body size. In contrast, sex differences in FPG and HbA 1c levels are likely to have a true physiological basis. In clinical practice, the HbA 1c assay may be more convenient than the OGTT, but it is important to note that different populations are identified by the two methods.Trial registration ClinicalTrials.gov NCT00289237

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“…The overflow hypothesis posits that, as the capacity of adipocytes to store fat is exceeded, lipids overflow into other tissues, particularly the liver and muscle [59]. Increasing levels of ectopic lipid infiltration correlate with insulin resistance and increase risk of type 2 diabetes [60,61]. Elevated free fatty acid levels, and the conversion of free fatty acids to long chain acyl CoA derivatives, results in reduced insulin signalling and glucose transport, as well as further insulin resistance in liver and muscle [62,63].…”

Section: Clinical Pathophysiologymentioning

confidence: 99%

Diabesity: therapeutic options

Colagiuri¹

2010

Diabetes Obesity Metabolism

102

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A pathogenic relationship exists between type 2 diabetes and obesity. Over the last decade, the escalation in diabetes cases has paralleled the rapid increase in obesity rates, constituting a global health crisis. Environmental risk factors attributed to the global increase in obesity include the consumption of high-calorie, high-fat foods and inadequate physical activity. Obese individuals may also have a genetic predisposition for obesity. Both diabetes and obesity confer an elevated risk of developing a range of complications and comorbidities, including cardiovascular disease, hypertension and stroke, which can complicate disease management. This review examines the aetiology of the linkages between diabetes and obesity and the range of available therapies. Recent clinical evidence substantiating the efficacy and safety of incretin-based antidiabetic therapies is analysed, in addition to data on antiobesity therapeutic strategies, such as antiobesity agents, behaviour modification and bariatric surgery. Glucose control is often accompanied by weight-neutral or modest weight reduction effects with DPP-4 inhibitor treatment (sitagliptin, vildagliptin, saxagliptin) and weight loss with GLP-1 receptor agonist therapy (exenatide, liraglutide). Studies of antiobesity agents including orlistat, sibutramine and rimonabant have shown attrition rates of 30-40%, and the long-term effects of these agents remain unknown. Bariatric surgical procedures commonly performed are laparoscopic adjustable banding of the stomach and the Roux-en-Y gastric bypass, and have produced type 2 diabetes remission rates of up to 73%. Therapeutic strategies that integrate glycaemic control and weight loss will assume greater importance as the prevalence of diabetes and obesity increase. Keywords: DPP-4, exenatide, GLP-1 analogue, human, incretin, liraglutide, once-daily, type 2 diabetes mellitus Date submitted 2 June 2009; date of first decision 2 November 2009; date of final acceptance 4 November 2009 IntroductionThe term 'diabesity', coined by Sims and colleagues [1] in the 1970s, describes the strong link between type 2 diabetes and obesity [1,2]. As evidence of this pathogenic interrelationship continues to accumulate, so does the appearance of the term in the clinical literature. A large body of clinical evidence attests to the relationship between being overweight or obese and being at an elevated risk for development of type 2 diabetes [3][4][5][6][7]. The risk escalates with the degree of excess weight, increasing threefold with a body mass index (BMI) of 25.0-29.9 kg/m 2 and 20-fold with a BMI over 30 kg/m 2 [4]. In particular, abdominal fat accumulation exacerbates insulin resistance and confers a strong, independent risk of developing diabetes [8]. Global diabetes prevalence is estimated at 171 million and is projected to more than double, to 366 million, by 2030 [9]. Countries with the highest numbers of diabetes cases include India, China, USA, Indonesia and Japan [9][10][11]. The greatest relative increases in diabetes incide...

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Insulin Sensitivity, Insulin Secretion, and Abdominal Fat

Cited by 276 publications

References 44 publications

Lack of association of liver fat with model parameters of β-cell function in men with impaired glucose tolerance and type 2 diabetes

Lack of association of liver fat with model parameters of β-cell function in men with impaired glucose tolerance and type 2 diabetes

Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study

Diabesity: therapeutic options

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