Diabetes Mellitus最新文献

Background/purpose: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline.

Subjects/methods: Using data from a large population of US adults with Hispanic ancestry, without known or unknown T2D at baseline (N=6,159), participants were classified as avocado consumers (N=983) or non-consumers (N=5,176) based on the mean of two 24-hour dietary recalls. Cox proportional hazard models estimated the association of avocado consumption with incident T2D (N=656 cases) over a six-year follow-up period, in the population as a whole, and separately in those with normoglycemia vs. prediabetes at baseline. A set of three sequential models were run: the first controlling only for sociodemographic factors ("minimally adjusted" models), the second for these and health behaviors ("fully adjusted" models), and a third for both sets of covariates and also body mass index (BMI; "fully adjusted + BMI" models).

Results: In the population as a whole, avocado intake at baseline was associated with reduced incident T2D in both the minimally adjusted (hazard ratio [HR] (+/- 95% confidence intervals [CIs]): 0.70 (0.52 - 0.94), P=.04) and the fully adjusted models (HR: 0.72 (0.54-0.97), P=.03). This association was observed in both those with prediabetes and with normoglycemia at baseline, but only reached significance in those with prediabetes (minimally adjusted model: HR: 0.68 (0.48-0.97), P=.03; fully adjusted model: HR: 0.69 (0.48-0.98), P=.04), not in those with normoglycemia (minimally adjusted model: HR: 0.86 (0.45-1.65), P=.65; fully adjusted model: HR: 0.80 (0.41-1.55), P=.50). In models which additionally controlled for BMI ("fully adjusted + BMI model"), the associations were slightly attenuated (overall population: HR: 0.79 (0.59-1.06), P=.60; normoglycemia: HR: 0.83 (0.42-1.64), P=.60; prediabetes: HR= 0.75 (0.54 - 1.05), P=0.09).

Conclusions: In our longitudinal analyses, adults with Hispanic / Latino ancestry who consumed avocado were less likely to develop T2D than those who did not consume avocado at baseline, especially if they had prediabetes at baseline.

Objective: The Life in BALANCE (LIB) study is a pilot translational study modeling the Diabetes Prevention Program (DPP) intensive lifestyle coaching intervention among an underserved, high-risk population: American Indians/Alaska Natives (AI/ANs) living in a large urban setting (Las Vegas, Nevada).

Research design and methods: A total of 22 overweight/obese AI/ANs (age, 39.6 ± 10.4 years; BMI, 34.1 ± 6.3 kg/m²) at increased risk for developing type 2 diabetes (HbA1c > 5.4 (36 mmol/mol) < 6.4 percent (46 mmol/mol) participated in the program between April and December, 2011. Study participants completed a 16 week intensive lifestyle coaching intervention. In addition to obtaining qualitative data regarding opportunities and challenges of applying the lifestyle intervention for AI/AN participants in an urban setting, clinical data, including BMI, waist circumference, blood pressure, fasting blood glucose, and blood lipids (HDL, LDL and Triglycerides), were collected.

Results: Only 12 of the 22 participants remained in the LIB program at the final post-program follow-up. Participants demonstrated significant decreased waist circumference and elevated HDL cholesterol. Triglycerides manifested the highest percentage change without statistical significance. No significant change was observed in blood pressure or fasting blood glucose.

Conclusions: LIB participants' improvements in BMI, waist circumference, HDL cholesterol and triglycerides suggests type 2 diabetes prevention programs aimed at urban AI/ANs show significant potential for reducing the risk of developing type 2 diabetes among this underserved and high risk community. Qualitative data suggest the main challenge for type 2 diabetes prevention specific to this population is a need for improved community outreach strategies.

Background: Increased mitogen-activated protein kinase (MAPK) phosphorylation has been detected in peripheral nerve of human subjects and animal models with diabetes as well as high-glucose exposed human Schwann cells, and have been implicated in diabetic peripheral neuropathy. In our recent studies, leukocytetype 12/15-lipoxygenase inhibition or gene deficiency alleviated large and small nerve fiber dysfunction, but not intraepidermal nerve fiber loss in streptozotocin-diabetic mice.

Methods: To address a mechanism we evaluated the potential for pharmacological 12/15-lipoxygenase inhibition to counteract excessive MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy. C57Bl6/J mice were made diabetic with streptozotocin and maintained with or without the 12/15-lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC). Human Schwann cells were cultured in 5.5 mM or 30 mM glucose with or without CDC.

Results: 12(S) HETE concentrations (ELISA), as well as 12/15-lipoxygenase expression and p38 MAPK, ERK, and SAPK/JNK phosphorylation (all by Western blot analysis) were increased in the peripheral nerve and spinal cord of diabetic mice as well as in high glucose-exposed human Schwann cells. CDC counteracted diabetes-induced increase in 12(S)HETE concentrations (a measure of 12/15-lipoxygenase activity), but not 12/15-lipoxygenase overexpression, in sciatic nerve and spinal cord. The inhibitor blunted excessive p38 MAPK and ERK, but not SAPK/ JNK, phosphorylation in sciatic nerve and high glucose exposed human Schwann cells, but did not affect MAPK, ERK, and SAPK/JNK phosphorylation in spinal cord.

Conclusion: 12/15-lipoxygenase inhibition counteracts diabetes related MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy and implies that 12/15-lipoxygenase inhibitors may be an effective treatment for diabetic peripheral neuropathy.

Objective: To profile the differential gene expression of the KEGG Adipocytokine Signaling pathway in omental compared to subcutaneous tissue in normal pregnancy.

Study design: Subjects included 14 nonobese, normal glucose tolerant, healthy pregnant women. Matched omental and subcutaneous tissue were obtained at elective cesarean delivery. Gene expression was evaluated using microarray and validated by RT-PCR. Differential gene expression was defined as ≥1.5 fold increase at p < 0.05.

Results: Six genes were significantly downregulated with two upregulated genes in omental tissue. Downregulation of Adiponectin and Insulin Receptor substrate, key genes mediating insulin sensitivity, were observed with borderline upregulation of GLUT-1. There were downregulations of CD36 and acyl-CoA Synthetase Long-chain Family Member 1which are genes involved in fatty acid uptake and activation. There was a novel expression of Carnitine palmitoyltransferase 1C.

Conclusion: Differential gene expression of Adipocytokine Signaling Pathway in omental relative to subcutaneous adipose tissue in normal pregnancy suggests a pattern of insulin resistance, hyperlipidemia, and inflammation.

Objective: Although abnormalities in the fatty acid composition of serum and red cell membrane phospholipids of patients with type 2 diabetes are well-documented, lacking are studies of this issue in prediabetic individuals.

Materials/methods: For this cross-sectional study, we recruited 180 subjects (30-80 years), 56 of whom were normal with regard to glucose control (HbA1c, <5.7%), 61 who had prediabetes (HbA1c, 5.7%-6.4%) and 59 who had type 2 diabetes (HbA1c, >6.5%). Serum phospholipids were isolated and analyzed for fatty acids.

Results: Most importantly, the fatty acid compositions of the controls and prediabetic subjects were not different for 19 fatty acids. However, the fatty acid profile of the phospholipids of the patients with diabetes differed from the other two groups; the 14 to 18-carbon saturated fatty acids were decreased by 12%-26% whereas the unsaturated fatty acids 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6 and 20:4n-6 were increased by 45%-64%. Of note, the docosahexaenoic acid (DHA) status of individuals in all three study groups was remarkably low compared with international values, as indicated by DHA proportions in the 1.62%-2.07% range, and there were no differences between groups. The mean melting point of the phospholipid fatty acids of the diabetic patients (32.2°C) was significantly lower (p < 0.001) than that of the prediabetic subjects (38.1°C) and the controls (39.9°C) which were not different from each other.

Conclusion: These observations indicate that the fatty acid changes associated with type 2 diabetes follow the onset of the disease as opposed to being a causative factor of poor glucose control and insulin insensitivity.

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.