Noninvasive Quantification of Pancreatic Fat in Humans

Lingvay, Ildiko; Esser, Victoria; Legendre, Jaime L.; Price, Angela; Wertz, Kristen M.; Adams‐Huet, Beverley; Zhang, Song; Unger, Roger H; Szczepaniak, Lidia S.

doi:10.1210/jc.2009-0584

Cited by 171 publications

(170 citation statements)

References 14 publications

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“…Using non-invasive spectroscopy, which has been shown to have good reliability and validity in adults [45], we observed significant pancreatic fat in the majority, but negligible pancreatic fat in two individuals. These pilot data may suggest that type 2 diabetes can manifest in youth without the presence of pancreatic fat, but more data concerning the association between pancreatic fat and metabolic health, and its response to therapeutic interventions, are required.…”

Section: Presence Of Type 2 Diabetes and Intra-organ Fat Reductionsmentioning

confidence: 80%

“…Furthermore, with no controls in this proof-of-concept trial, a bigger study, with an appropriate control sample, is needed to confirm our findings. Although the 1 H-MRS approach used for pancreatic fat quantification has been shown to be reliable [45], results can be confounded by respiratory movement. Therefore, it is inappropriate to conclude on the efficacy of dietary intervention for pancreatic fat modification from this small pilot study.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study

et al. 2016

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Aims/hypothesis The aim of the study was to investigate whether a very-low-energy diet (VLED) is a feasible and acceptable treatment option for type 2 diabetes in children and adolescents, and whether adherence can lead to rapid weight loss, reversal of type 2 diabetes and reduced liver fat as seen in adult studies. Methods Eight participants with type 2 diabetes and obesity, aged 7-16 years, non-medicated (n = 1) or treated with metformin (n = 7) and in some cases insulin (n = 3), followed a VLED (<3360 kJ/day) for 8 weeks, then transitioned to a hypocaloric diet (∼6300 kJ/day) that they followed to 34 weeks. HbA 1c , fasting glucose and 2 h post-glucose load plasma glucose (2hG) were determined from fasting blood and an OGTT. Liver fat concentration was quantified using proton magnetic resonance spectroscopy. Adherence was defined as ≥5% weight loss during the 8 week VLED. Results Adherers (n = 5) and non-adherers (n = 3) had median weight loss of 7.5% and 0.5%, respectively, at 8 weeks. Only three out of eight participants met non-alcoholic fatty liver disease (NAFLD) criteria (≥5.5%) at 8 weeks, compared with eight out of eight at baseline. The three participants on insulin therapy at baseline were able to cease therapy during the 8 week VLED. At 34 weeks, adherers (n = 5) achieved 12.3% weight loss, none met NAFLD criteria and four did not meet American Diabetes Association criteria for type 2 diabetes.

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Section: Presence Of Type 2 Diabetes and Intra-organ Fat Reductionsmentioning

confidence: 80%

Section: Strengths and Limitationsmentioning

confidence: 99%

Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study

et al. 2016

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“…The mechanism of such GI alkali loss and its association with type 2 diabetes has not yet been investigated. One potential mechanism is pancreatic fat accumulation described in individuals with type 2 diabetes (18,19), which could influence pancreatic exocrine function and bicarbonate secretion, resulting in GI alkali loss. Alternatively, differences in gut microbiota (20) or longer colonic transit time in patients with type 2 diabetes (21) could lead to more bacterial fermentation of colonic content and secondarily to greater organic anion generation and absorption.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Basis for Low Urine pH in Type 2 Diabetes

Maalouf

Cameron

Moe³

et al. 2010

Clinical Journal of the American Society of Nephrology

130

113

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Background and objectives: Type 2 diabetes is associated with excessively low urine pH, which increases the risk for uric acid nephrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes.Design, setting, participants, & measurements: Nine non-stone-forming patients who had type 2 diabetes and low urine pH and 16 age-and body mass index-matched non-stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour urine was collected on the last 2 days of the diet.Results: Urine dietary markers (potassium, sulfate, phosphorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour urine pH (5.45 ؎ 0.27 versus 5.90 ؎ 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ؎ 12 versus 38 ؎ 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH 4 ؉ /NAE) was significantly lower in patients with type 2 diabetes than in control subjects

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“…The role of pancreatic steatosis in the pathogenesis of type 2 diabetes is currently under discussion and may depend on additional risk factors [1][2][3]. Fat accumulation in the pancreas is associated with reduced insulin secretion in glucose intolerant humans [4].…”

Section: Introductionmentioning

confidence: 99%

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

et al. 2017

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Aims/hypothesis Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. Methods Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68. Pancreatic adipocytes were identified by Oil Red O and adiponectin staining.Primary pancreatic pre-adipocytes and differentiated adipocytes were co-cultured with human islets isolated from organ donors and the metabolic crosstalk between fatty liver and fatty pancreas was mimicked by the addition of palmitate and fetuin-A. Insulin secretion was evaluated by ELISA and RIA. Cytokine expression and secretion were assessed by RT-PCR and multiplex assay, respectively. Subcellular distribution of proteins was examined by confocal microscopy and protein phosphorylation by western blotting. Results In human pancreatic parenchyma, highly differentiated adipocytes were detected in the proximity of islets with normal architecture and hormone distribution. Infiltration of adipocytes was associated with an increased number of CD68-positive cells within islets. In isolated primary pancreatic preadipocytes and differentiated adipocytes, palmitate and fetuin-A induced IL6, CXCL8 and CCL2 mRNA expression. Cytokine production was toll-like receptor 4 (TLR4)-dependent and further accentuated in pre-adipocytes when cocultured with islets. In islets, IL6 and CXCL8 mRNA levels were also increased by fetuin-A and palmitate. Only in macrophages within the isolated islets, palmitate and fetuin-A stimulated the production of the cytotoxic cytokine IL-1β. Palmitate, but not fetuin-A, exerted pro-apoptotic effects in islet cells. Instead, fetuin-A impaired glucose-induced insulin secretion in a TLR4-independent, but c-Jun N-terminal kinase-and Ca 2+ -dependent, manner. Conclusions/interpretation These results provide the first evidence that fetuin-A-mediated metabolic crosstalk of fatty liver with islets may contribute to obesity-linked glucose blindness of beta cells, while fatty pancreas may exacerbate local inflammation.

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Noninvasive Quantification of Pancreatic Fat in Humans

Cited by 171 publications

References 14 publications

Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study

Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study

Metabolic Basis for Low Urine pH in Type 2 Diabetes

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

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