Longitudinal dynamics of body weight change in the development of type 2 diabetes

Hansen, Barbara C.; Newcomb, Jennifer D.; Ren, Chao; Linden, Ellen H.

doi:10.1002/oby.20292

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…A long history of studying nonhuman primates for translational research in T2D, and the most commonly used species include rhesus macaques ( Macaca mulatta ), cynomolgus monkeys ( Macaca fascicularis ), baboons ( Papio species ), African Green Monkeys ( Chlorocebus species ), and common marmosets ( Callithrix jacchus ) [32]. A number of models are in use for the study of T2D in nonhuman primates, including high fructose-fed nonhuman primate models [33], diet-induced nonhuman primate models [34], and aged-spontaneous T2D nonhuman primate models [35]. The presence of islet amyloidosis, IR to β-cell failure, and overt diabetes mellitus characteristic of T2D in humans is also observed in diabetic monkeys, implicating a similar etiology of islet lesions in monkeys and humans [36,37].…”

Section: Animal Models Of T2dmentioning

confidence: 99%

In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity

et al. 2019

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About 40% of the world’s population is overweight or obese and exist at risk of developing type 2 diabetes mellitus (T2D). Obesity is a leading pathogenic factor for developing insulin resistance (IR). It is well established that IR and a progressive decline in functional β-cell mass are hallmarks of developing T2D. In order to mitigate the global prevalence of T2D, we must carefully select the appropriate animal models to explore the cellular and molecular mechanisms of T2D, and to optimize novel therapeutics for their safe use in humans. Flavonoids, a group of polyphenols, have drawn great interest for their various health benefits, and have been identified in naturally occurring anti-diabetic compounds. Results from many clinical and animal studies demonstrate that dietary intake of flavonoids might prove helpful in preventing T2D. In this review, we discuss the currently available rodent animal models of T2D and analyze the advantages, the limitations of each T2D model, and highlight the potential anti-diabetic effects of flavonoids as well as the mechanisms of their actions.

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Section: Animal Models Of T2dmentioning

confidence: 99%

In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity

et al. 2019

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“…Li Gong et al [16] reported the classification and diagnosis of T2DM in the rhesus monkey subspecies Macaca mulatta lasiotis , which was used in the present study. Like humans, the NHPs have an increased likelihood of developing obesity and T2DM with increasing age [25]. Monkeys in this study lived in a highly controlled and stable environment, and their metabolic histories were well documented.…”

Section: Discussionmentioning

confidence: 99%

MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys

Zhang

Zeng²,

Chen

et al. 2019

Eur Radiol

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Objective To detect diffuse myocardial fibrosis in different severity levels of left ventricular diastolic dysfunction (DD) in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys. Methods Eighteen spontaneous T2DM and nine healthy monkeys were studied. Echocardiography was performed for diastolic function classification. Cardiac magnetic resonance (CMR) imaging was performed to obtain extracellular volume fraction (ECV) maps and T1ρ maps at two different spin-locking frequencies. ECV values, T1ρ values, and myocardial fibrosis index (mFI) values which are based on the dispersion of T1ρ, were calculated. Global peak diastolic longitudinal strain rates (GSrL) were also obtained. Results Echocardiography results showed mild DD in nine T2DM monkeys and moderate DD in the other nine. The global ECV values were significantly different among healthy animals as compared with animals with mild DD or moderate DD, and the ECV values of animals with moderate DD were significantly higher as compared with those of mild DD. The mFI values increased progressively from healthy animals to those with mild DD and then to those with moderate DD. Diastolic function indicators (e.g., early diastolic mitral annulus velocity, GSrL) correlated well with ECV and mFI. Conclusions Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. T1ρ mapping may have the potential to be used for diffuse myocardial fibrosis assessment. Key Points • Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen . • The relationship between diastolic dysfunction and diffuse myocardial fibrosis may be demonstrated by imaging markers . • Non-contrast T1ρ mapping may have the potential to be used for diffuse myocardial assessment . Electronic supplementary material The online version of this article (10.1007/s00330-018-5950-9) contains supplementary material, which is available to authorized users.

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“…Our monkey cohort is comprised of animals from multiple institutions with variable environments that may have influenced disease risk. The average age of T2DM diagnosis was 19 years, with the youngest onset of diabetes reported at 10 years old in a large T2DM rhesus macaque colony (39). Our monkeys were on average 11.5 years old and thus diabetes prevalence would be expected to be very low.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

et al. 2015

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One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5–8.4 Gy) 5–9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertriglyceridemia, however, they lack the typical obese presentation of primate midlife diabetogenesis. Surprisingly, body composition analyses by computed tomography indicated that prior irradiation led to a specific loss of visceral fat mass. Prior irradiation led to reductions in insulin signaling effectiveness in skeletal muscle and higher monocyte chemoattractant protein 1 levels, indicative of increased inflammation. However, there was an absence of large defects in pancreatic function with radiation exposure, which has been documented previously in animal and human studies. Monkeys that remained healthy and did not become diabetic in the years after irradiation were significantly leaner and smaller, and were generally smaller and younger at the time of exposure. Irradiation also resulted in smaller stature in both diabetic and nondiabetic monkeys, compared to nonirradiated age-matched controls. Our study demonstrates that diabetogenesis postirradiation is not a consequence of disrupted adipose accumulation (generalized or in ectopic depots), nor generalized pancreatic failure, but suggests that peripheral tissues such as the musculature are impaired in their response to insulin exposure. Ongoing inflammation in these animals appears to be a consequence of radiation exposure and can interfere with insulin signaling. The reasons that some animals remain protected from diabetes as a late effect of irradiation are not clear, but may be related to body size. The translational relevance for these results suggest that muscle may be an important and underappreciated target organ for the delayed late effect of whole-body irradiation, leading to increased risk of insulin resistance and diabetes development.

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Longitudinal dynamics of body weight change in the development of type 2 diabetes

Cited by 10 publications

References 24 publications

In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity

In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity

MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys

Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

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