Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy

The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiota composition and function can directly impact the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged as a potential source of novel therapeutics, strongly modulates host immunity and metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl sulfate, trimethylamine?N?oxide) dictate a secretory associated senescence phenotype and chronic low-grade inflammation, features shared in the physiological process of ageing (“inflammaging”) as well as in T2DM (“metaflammation”) and in its microvascular complications. This review provides an in-depth look on the crosstalk between GM, host immunity and metabolism. Further, it characterizes human GM signatures of elderly and T2DM patients. Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic changes) underlying causal relationships between GM dysbiosis and diabetic retinopathy/nephropathy complications is pinpointed, with the ultimate goal to unravel potential pathophysiological mechanisms that may be explored, in a near future, as personalized disease-modifying therapeutic approaches.     

Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population

In this study we examined the association of adiponectin gene variants with circulating adiponectin, and known metabolic diseases in 298 healthy controls and 297 Saudi subjects with type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters were measured by standard procedures. Genotyping of T45G and G276T single nucleotide polymorphisms of adiponectin gene was carried out by PCR-RFLP analysis. No significant differences in the genotype distribution of T45G and G276T polymorphism were found between control and diabetic subjects. Neither SNP conferred an association with T2DM, obesity, hypertension or dyslipidemia. Despite a marked decrease in patients as opposed to controls, adiponectin levels were not different according to genotypes of T45G and G276T polymorphisms in control and patients. Thus, neither adiponectin SNPs independently conferred increased T2DM risk nor in other metabolic conditions considered such as obesity, hypertension or dyslipidemia. These findings support the existence of population based differences in the association of adiponectin gene variants with metabolic phenotypes and emphasize the importance of studying multiple polymorphisms, sufficient enough to identify the adiponectin gene as a genetic marker for several non-chronic communicable diseases.     

Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance

To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.     

Polar lipid derangements in type 2 diabetes mellitus: potential pathological relevance of fatty acyl heterogeneity in sphingolipids

While pathological alterations in plasma neutral lipids with type 2 diabetes mellitus (T2DM) has been relatively well-characterized, only limited information is available on the variations in global polar lipidome (glycerophospholipids and sphingolipids) with the disease. To systematically identify polar lipid aberrations associated with early stage T2DM, we quantitatively profiled and compared changes in more than 300 plasma lipid species from distinct groups of T2DM patients against overtly healthy controls. Sphingolipid classes including ceramides, sphingomyelins, lactosylceramides (LacCer) and ganglioside GM3 (GM3) were significantly elevated in mild T2DM with a concomitant decrease in glucosylceramides (GluCer), suggesting the increased conversion of GluCer to LacCer in mild diabetes. Individual GM3 species were altered in T2DM according to their acyl chain lengths. While long-chain GM3s (fatty acyl carbon ≥18) were significantly increased in T2DM, the opposite was observed for GM3 18:1/16:0. Importantly, long-chain GM3 species were negatively correlated with HOMA2-%β and positively correlated with FBG; and could distinguish between healthy individuals and mildly diabetic patients with similar HOMA2-%β. The current study therefore identifies metabolic alterations in sphingolipid pathways as early events in T2DM pathogenesis, and provides hypothesis-generating new insights relevant for larger scale clinical studies aimed at identification of early molecular markers of T2DM.     

Serum metabolic signatures of fulminant type 1 diabetes

Fulminant type 1 diabetes (FT1DM) is a relatively new clinical entity featured by acute destruction of pancreatic beta cells. Clinical consequences of FT1DM could be fatal when timely medications are not provided, suggesting the particular importance of rapid and accurate diagnosis. Here we report a serum metabonomics study of FT1DM patients, together with healthy control subjects (NC), type 2 diabetes (T2DM), classic type 1 diabetes (T1DM), and diabetic ketoacidosis (DKA) patients, with the aim of discovering metabolic markers associated with FT1DM. A total of 79 subjects were enrolled (22 NC, 22 T1DM, 22 T2DM, 8 DKA and 5 FT1DM) and the serum metabolic profiling of fasting blood samples was performed using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) coupled with multivariate and univariate statistical analyses. Serum metabolites differentially expressed in FT1DM relative to NC, or to T2DM, T1DM and DKA were identified. Three metabolite markers, 5-oxoproline, glutamate, and homocysteine, were significantly altered among FT1DM, T2DM, T1DM, and DKA. In addition, the three metabolite markers, 5-oxoproline, glutamate, and homocysteine, presented similar patterns of distribution across groups. The results showed that the metabolic signatures of FT1DM identified in this study could be of potential clinical significance for the accurate diagnosis of FT1DM.     

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Toll-like receptor 4 D299G polymorphism in metabolic disorders: a meta-analysis

The toll-like receptor 4 (TLR4) plays a key role in the activation of innate immune response participating in the recognition of lipopolysaccharides. Changes in the innate immune response are involved in the pathogenesis of some metabolic disorders such as metabolic syndrome and type 2 diabetes mellitus (Met-S and T2DM). It has been recently shown the role of gut microbiota in the perpetuation of both insulin resistance and low-grade chronic inflammation. Some studies have reported that TLR4 D299G polymorphism is associated with metabolic disorders, however results have been inconsistent. Two recent meta-analyses showed that D299G is associated with inflammatory bowel disease and gastrointestinal cancers risk, two pathological states in which the luminal microbial flora-host cells interaction may be implicated. We conducted a systemic review of the published data considering all eligible published studies (six studies with 1696 cases and 3388 controls for D299G) and a meta-analysis was performed to evaluate the association between TLR4 D299G polymorphism and the risk for metabolic disorders. Five studies were identified for T2DM: three corresponding to Caucasian populations and two to mixed populations. The remaining study analyzed Met-S in a Caucasian population. We observed a significant association between D299G polymorphism and metabolic disorders (T2DM and Met-S) risk (OR = 0.566, 95 % CI: 0.347–0.925, p = 0.023) particularly in Caucasians. No association was found in mixed population subgroup. Our meta-analysis identified that the AG/GG genotypes of D299G are associated with decreased metabolic disorders risk.     

Prevalence of Hypogonadism in Patients with Type 2 Diabetes Mellitus in an Asian Indian Study Group

ObjectiveTo determine the prevalence of hypogonadism in Asian Indian patients with type 2 diabetes mellitus (T2DM) and to correlate it with components of the metabolic syndrome and microvascular complications of T2DM.MethodsOne hundred consecutive male patients with T2DM between 25 and 50 years of age and 50 age-matched healthy adults without diabetes underwent assessment. Calculated free testosterone was derived by using serum total testosterone and sex hormone-binding globulin. Those patients with 2 calculated free testosterone values less than 64.8 pg/mL were diagnosed as having hypogonadism.ResultsOf the 100 patients with T2DM, 15 (15%) were found to have hypogonadism—7 of 29 (24%) between 31 and 40 years of age and 8 of 67 (12%) between 41 and 50 years old. None of the 4 patients between 25 and 30 years old had hypogonadism. Eleven patients (73%) had hypogonadotropic hypogonadism, and 4 (27%) had hypergonadotropic hypogonadism. Among the control subjects, the prevalence of hypogonadism was 10%. In comparison with Western data, we found a higher prevalence of hypogonadism in patients with T2DM, especially in those in the 4th decade of life. The prevalence of hypogonadism was higher in obese patients, although it did not reach statistical significance. No statistically significant correlation was observed between hypogonadism and age, duration of diabetes, glycemic control, androgen deficiency symptoms, or microvascular complications.ConclusionThe prevalence of hypogonadism was higher in the patients with diabetes than in the control subjects, although the difference did not reach statistical significance. There was no correlation of hypogonadism with components of the metabolic syndrome or microvascular complications of diabetes mellitus. (Endocr Pract. 2009;15:513-520)     

Lower wall shear rate of the common carotid artery in treated type 2 diabetes mellitus with metabolic syndrome

Arterial sites with low wall shear stress (WSS) are more prone to the development of atherosclerotic plaques, as was observed in carotid arteries in subjects with atherosclerosis risk factors. Type 2 diabetes mellitus (DM), hypertension, hyperlipidemia and other components of the metabolic syndrome, are associated with high risk for symptomatic cerebrovascular disease. It was shown by others that untreated type 2 DM is associated with lower WSS in common carotid arteries. However, the cardiovascular risk of type 2 DM could be modified by therapy. The aim of our study was to test the hypothesis that treated type 2 DM subjects with metabolic syndrome still have lower WSS in common carotid arteries than healthy controls. We enrolled 26 compensated DM subjects with metabolic syndrome, treated by metformin, statins and ACEI for more than 6 months, and 22 aged-comparable healthy controls. Wall shear rate (WSR) was used as a measure of WSS. A linear 3-11 MHz probe was used to measure blood velocity and internal diameter in the common carotid arteries. We compared observed values of WSR adjusted for age by ANCOVA. Wall shear rate was significantly lower in DM group than in control subjects: peak (systolic) values of wall shear rate were 410+/-130 s(-1) vs. 487+/-111 s(-1) (p<0.005). DM subjects had significantly lower WSR, because of both thinner lumen and slower blood flow velocities. Lower WSR was accompanied by higher IMT (0.73+/-0.12 mm vs. 0.64+/-0.11 mm, p<0.001). Treated subjects with compensated type 2 DM with metabolic syndrome still have atherogenic hemodynamic profile. These findings might help to understand faster progression of atherosclerosis in diabetic subjects with metabolic syndrome despite up-to-date medication.     

RT-qPCR assay on the vitamin D receptor gene in type 2 diabetes and hypertension patients in Turkey

RT-qPCR was used to analyze the vitamin D receptor (VDR) gene TaqI polymorphism in 100 Turkish patients with type 2 diabetes mellitus (T2DM) and hypertension compared with 100 healthy subjects, to determine whether VDR could be considered as one of the susceptibility genes for T2DM and hypertension. Genotyping was done with PCR, followed by melting curve analysis with specific fluorescent hybridization probes. The results showed that distributions for TT, Tt and tt genotypes were 51, 46 and 3% in the patient group, and 35, 49 and 16% in the control group, respectively. The frequency of the T allele in patients was also significantly higher than that in controls. Based on the results, the relationship between the VDR gene TaqI polymorphism and T2DM patients in the Turkish population was compared. In terms of the genotype distributions and allele frequencies of the VDR gene TaqI polymorphism, there was no statistically significant difference (P > 0.05) between the T2DM and hypertension patients and controls. Application of RT-qPCR method enabled us to assess the prevalence of the VDR gene TaqI polymorphism and its association with type 2 diabetes and hypertension.     

Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy

A considerable variability in the incidence and prevalence of diabetic nephropathy (DN) coheres with an important contribution of multigenetic predisposition in the development of DN. Some genes, which probably participate in the pathogenesis of diabetic nephropathy, also play a role in the regulation of blood pressure, familial hyperlipidemia, familial hypertension and other diseases of the cardiovascular system. We have examined the association of diabetic nephropathy, nephropathy of non-diabetic origin, hypertension and of type 2 diabetes itself with several genetic polymorphisms (the insertion/deletion polymorphism in the gene for angiotensin-converting enzyme, the G/T polymorphism in the glucose transporter 1 gene, the G/T (894) polymorphism and the T/C (−786) polymorphism in the eNOS gene in three groups of patients with diabetes mellitus: 1) patients without diabetic nephropathy (DM); 2) patients with DN; 3) patients with nephropathy of non-diabetic origin (NDRD). Angiotensin-converting enzyme is an important factor in a development of arterial hypertension, but in our groups of Central European diabetic patients the I/D polymorphism was not associated with diabetic nephropathy. Furthermore, we have confirmed that the T/C (T786C) polymorphism in the eNOS gene is associated with metabolic syndrome including type 2 diabetes.     

Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype

Over the past decade, emerging evidence has linked alterations in the gut microbial composition to a wide range of diseases including obesity, type 2 diabetes, and cardiovascular disease. Toll-like receptors (TLRs) are the major mediators for the interactions between gut microbiota and host innate immune system, which is involved in the localization and structuring of host gut microbiota. A previous study found that TLR5 deficient mice (TLR5KO1) had altered gut microbial composition which led to the development of metabolic syndrome including hyperlipidemia, hypertension, insulin resistance and increased adiposity. In the current study, a second TLR5-deficient mouse model was studied (TLR5KO2). TLR5 deficient mice did not manifest metabolic abnormalities related to the metabolic syndrome compared with littermate controls maintained on normal chow or after feeding a high fat diet. Analysis of the gut microbial composition of littermate TLR5KO2 and wild type mice revealed no significant difference in the overall microbiota structure between genotypes. However, the TLR5KO2 microbiota was distinctly different from that previously reported for TLR5KO1 mice with metabolic syndrome. We conclude that an altered composition of the microbiota in a given environment can result in metabolic syndrome, but it is not a consequence of TLR5 deficiency per se.     

基于肠道微生态探讨黄连素在代谢性疾病中的抗炎作用

肠道菌群与能量代谢密切相关,其组成和代谢紊乱可通过多种途径导致胰岛素抵抗,肥胖和2型糖尿病。黄连素因具有减重、降糖、调脂等作用被广泛用于肥胖、2型糖尿病及非酒精性脂肪性肝病等代谢性疾病的辅助治疗;研究表明,黄连素可调节肠道菌群的组成和代谢,改善肠道微生态环境,从而改善胰岛素抵抗和代谢。本文综述了黄连素通过肠道菌群-炎症轴在干预代谢性疾病的研究进展,以期为代谢性疾病的治疗寻找新的策略,并为今后该领域的深入研究提供指导意义。     

彩色多普勒超声诊断不同病程老年2型糖尿病下肢血管病变的临床价值及与血清ET、NO的关系研究

摘要 目的：探讨彩色多普勒超声诊断不同病程老年2型糖尿病(T2DM)下肢血管病变(LEADDP)的临床价值及与血清内皮素(ET)、一氧化氮(NO)的关系。方法：选取我院于2019年5月~2020年4月期间收治的80例老年T2DM合并LEADDP患者为观察组,根据不同病程分为3组,<10年组30例,10~20年组33例,>20年组17例,另选取同时期我院收治的50名老年单纯T2DM患者为对照组,所有受检者均接受彩色多普勒超声检查,并检测血清ET、NO水平。对比观察组与对照组足背动脉狭窄发生率,对比不同病程患者LEADDP检出率,对比不同病程患者及对照组的动脉血管内径、动脉血流量及血清ET、NO水平,Pearson相关性分析动脉血管内径、动脉血流量与血清ET和NO水平的相关性。结果：观察组足背动脉狭窄发生率明显高于对照组(P<0.05);不同病程患者LEADDP检出率随着病程延长而增加(P<0.05);不同病程患者动脉血管内径、动脉血流量、NO水平随着病程的的延长而降低,ET水平随着病程的延长而升高(P<0.05);Pearson相关性分析显示,动脉血管内径、动脉血流量与血清ET水平呈负相关,与NO水平呈正相关(P<0.05)。结论：老年T2DM合并LEADDP患者存在明显的下肢动脉管径狭窄和血流量缓慢,病变程度随着病程延长而增加,与血清ET、NO水平有密切关系,彩色多普勒超声诊断可有效评价其病变程度。     

Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy

Many of the immune and metabolic changes occurring during normal pregnancy also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in nonpregnant hosts. Here, to explore their role in pregnancy, we characterized fecal bacteria of 91 pregnant women of varying prepregnancy BMIs and gestational diabetes status and their infants. Similarities between infant-mother microbiotas increased with children's age, and the infant microbiota was unaffected by mother's health status. Gut microbiota changed dramatically from first (T1) to third (T3) trimesters, with vast expansion of diversity between mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced richness. T3 stool showed strongest signs of inflammation and energy loss; however, microbiome gene repertoires were constant between trimesters. When transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Our findings indicate that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy.     

Binge-Eating Disorder and Type 2 Diabetes: A Review

ObjectiveTo familiarize health care providers with diagnosis and treatment of binge-eating disorder (BED), a common comorbidity of type 2 diabetes (T2DM).MethodsLiterature review of binge eating and T2DM. Key words used in search include BED, T2DM, obesity, and treatment.ResultsThe prevalence of BED in patients with T2DM appears to be much higher than the 2% to 3.5% prevalence seen in the general population. Studies suggest that up to 20% of patients with T2DM have an underlying eating disorder, the most common of which is binge eating. BED is probably underdiagnosed, even though there are multiple simple tools that providers can use to improve screening for the disorder. Though the relationship between BED and hemoglobin A1c control can vary, it appears that binge-eating behaviors can worsen metabolic markers, including glycemic control. Various medications used by patients with diabetes have been associated with new-onset BED, and treatment may be as simple as removing or replacing such agents. Several medications have been found to significantly reduce binge-eating frequency, and potentially, weight. Patients with BED generally benefit from psychotherapy, including cognitive behavioral therapy.ConclusionBED, only recently added to the International Classification of Disease-10 diagnostic list, is very common in patients with obesity and T2DM. The diagnosis is important to establish, as treatment or referral for treatment, could potentially improve many of the comorbidities and metrics of T2DM.     

Hypertension associated with neurocognitive performance among persons with type 2 diabetes: a brief report

Background Among persons with type 2 diabetes (T2DM) it is not known whether the presence of hypertension could have a detrimental effect on learning ability and whether repeated exposure to information changes the amount of information retained. The aim of this study was to determine cross-sectional evidence for a differential burden to cognitive functioning among persons with T2DM and comorbid hypertension (HTN).Methods This study performed a cross-sectional, retrospective analysis, by medical chart review, of patients with a diagnosis of T2DM.Results Medical records information for history of HTN, age, gender and cognitive performance scores were recorded and analysed for 112 T2DM patients, with an average age of 60 years (SD = 13.84). Differences in cognitive performance scores were compared between patients with and without a history of HTN. The results show that participants who were diagnosed with hypertension produced lower average Rey Auditory–Verbal Learning Test scores than individuals who are not diagnosed with hypertension. Trial 2 was the only trial to prove significant with a P-value of 0.041.Conclusions Our results support previous studies showing that HTN is associated with increased risk to learning and memory functioning, although the degree of interference with these cognitive functions could not be determined from our research. Recognising that people diagnosed with HTN may be at risk for poorer learning and memory skills, future research can investigate how the length of time with the diseases affects learning and memory, and how medication management can attenuate cognitive learning and memory performance.     

Vitamin D and Prebiotics may benefit The Intestinal Microbacteria and improve Glucose Homeostasis in Prediabetes and Type 2 Diabetes

ObjectiveTo review the role of human large bowel microbacteria (microbiota) in the glucose homeostasis, to address vitamin D (VD) and prebiotics interactions with microbiota, and to summarize recent randomized clinical trials (RCTs) of VD and prebiotics supplementation in prediabetes (PreDM) and type 2 diabetes mellitus (T2DM).MethodsPrimary literature was reviewed in the following areas: composition and activity of human microbiota associated with PreDM and T2DM, interactions between microbiota and glucose homeostasis, the interaction of microbiota with VD/prebiotics, and RCTs of VD/prebiotics in subjects with PreDM or T2DM.ResultsThe human microbiota is comprised of 100 trillion bacteria with an aggregate genome that is 150-fold larger than the human genome. Data from the animal models and human studies reveal that an “obesogenic” diet results into the initial event of microbiota transformation from symbiosis to dysbiosis. The microbial antigens, such as Gram(-) bacteria and lipopolysaccharide (LPS), translocate to the host interior and trigger increased energy harvesting and Toll-like receptor (TLR) activation with subsequent inflammatory pathways signaling. The “double hit” of steatosis (ectopic fat accumulation) and “—itis” (inflammation) and contribution of “corisks” (e.g., vitamin D deficiency [VDD]) are required to activate molecular signaling, including impaired insulin signaling and secretion, that ends with T2DM and associated diseases. Dietary changes (e.g., prebiotics, VD supplementation) may ameliorate this process if initiated prior to the process becoming irreversible.ConclusionEmerging evidence suggests an important role of microbiota in glucose homeostasis. VD supplementation and prebiotics may be useful in managing PreDM and T2DM. (Endocr Pract. 2013;19:497-510)     

Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus.

Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T(or) between groups (P > 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 +/- 0.07 degrees C in controls and 36.55 +/- 0.05 degrees C in T2DM patients (P < 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P > 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM.     

Dietary fibers as emerging nutritional factors against diabetes: focus on the involvement of gut microbiota

Diabetes mellitus (DM) increases the risk of cardiovascular diseases and other secondary complications, such as nephropathy, neuropathy, retinopathy, etc. The important risk factors for the pathogenesis of DM are aging, family history, sedentary lifestyle, unhealthy dietary habits, and obesity. Evidence from epidemiological studies also indicates that DM is characterized by specific alterations in the human gut microbiota (GM). GM transplantation in rodents and humans revealed that a specific GM constituent can be the cause and not just the consequence of the DM condition and complications. These findings suggest a potential role of GM in human health, disease prevention, and treatment. Dietary intervention studies using dietary fibers (DFs) suggested that modulation of the GM can suppress the metabolic risk markers in humans. However, a causal role of GM in such studies remains unexplored. Long-term follow-up studies disclosed that the diet rich in insoluble and non-viscous fibers are responsible for DF-mediated antidiabetic activities, while soluble and viscous fibers have little influence on DM despite having a profound impact on glycemia. However, general conclusions cannot be drawn simply based on these findings. Long-term follow-up studies are urgently required in this area to explore the therapeutic potential of different DFs in treating DM and to delineate the exact role of GM involvement. Here we review and discuss the signature of GM during DM, antidiabetic activity of metformin via GM modulation, DFs from different sources and their antidiabetic activity, and the possible role of GM involvement.