Food intake and dietary glycaemic index in free-living adults with and without type 2 diabetes mellitus

A recent Cochrane review concluded that low glycaemic index (GI) diets are beneficial in glycaemic control for patients with type 2 diabetes mellitus (T2DM). There are limited UK data regarding the dietary GI in free-living adults with and without T2DM. We measured the energy and macronutrient intake and the dietary GI in a group (n = 19) of individuals with diet controlled T2DM and a group (n = 19) without diabetes, matched for age, BMI and gender. Subjects completed a three-day weighed dietary record. Patients with T2DM consumed more daily portions of wholegrains (2.3 vs. 1.1, P = 0.003), more dietary fibre (32.1 vs. 20.9 g, P < 0.001) and had a lower diet GI (53.5 vs. 57.7, P = 0.009) than subjects without T2DM. Both groups had elevated fat and salt intake and low fruit and vegetable intake, relative to current UK recommendations. CONCLUSIONS: Patients with T2DM may already consume a lower GI diet than the general population but further efforts are needed to reduce dietary GI and achieve other nutrient targets.     

Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2

Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted by specialised gut cells. GLP-1 is also produced in the pancreatic islets and the central nervous system. Both incretins bind to specific G-protein-coupled receptors that are distributed throughout the body. Incretins potentiate meal-induced insulin production and secretion by the beta-cells and lower the blood glucose level in the presence of hyperglycaemia. GLP-1 and GIP stimulate beta-cell proliferation and differentiation, whereas GLP-1 only inhibits gastric emptying and glucagon secretion, reduces food intake and improves insulin sensitivity. Insulin-resistant and type-2 diabetic patients have an impaired incretin response to meal ingestion. However, the insulinotropic action of exogenous GLP-1, but not that of GIP, is preserved in these subjects. After parenteral administration, GLP-1 has an extremely short duration of action because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV (DPPIV). To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived from the Gila monster hormone exendin-4, have been developed. Enhancement of incretin action seems a rational and promising option for the treatment of type-2 diabetes.     

Empirical dietary inflammatory pattern and metabolic syndrome: prospective association in participants with and without type 1 diabetes mellitus in the coronary artery calcification in type 1 diabetes (CACTI) study

The inflammatory potential of diet, assessed by Empirical Dietary Inflammatory Pattern (EDIP), may play a crucial role in the development of metabolic syndrome (MetS). However, limited research on this relationship is available. We hypothesized that EDIP is positively associated with MetS and its components. This longitudinal study included 1177 participants (526 with type 1 diabetes mellitus [T1DM] and 651 without) from the Coronary Artery Calcification in Type 1 Diabetes study. Dietary assessment and anthropometric and biochemical measurements were assessed at baseline and 14-year follow-up. MetS status was defined using the Harmonization criteria. EDIP scores were computed based on a food frequency questionnaire. Generalized linear mixed models were applied and subgroup analyses were performed by diabetes status. Mean age of study participants was 38 years and 48% were male at baseline. EDIP was positively associated with MetS (β_{T3 versus T1}=0.81, P < .01) in T1DM but not in nondiabetic controls. Of the MetS components, low HDL-C and hypertriglyceridemia had positive associations with EDIP in both groups. Individuals with T1DM consumed more pro-inflammatory diets and had a greater risk of developing MetS than those without diabetes. The consumption of processed meat, red meat, high- and low- energy beverages was significantly higher in those with MetS than those without this condition (all P < .05). Reduced consumption of pro-inflammatory foods such as processed meat, red meat, sugar-sweetened beverages, and diet drinks may lower MetS risk in T1DM.     

Effect of large bowel fermentation on insulin, glucose, free fatty acids, and glucagon-like peptide 1 (7-36) amide in patients with coronary heart disease

Insulin resistance syndrome has recently been described as a unifying hypothesis to explain the relationship between the many risk factors of coronary heart disease. Carbohydrate that is malabsorbed and fermented in the colon has been demonstrated to decrease insulin response to a glucose load and improve other risk factors associated with coronary heart disease, although the mechanism remains unclear. The object of the present study was to investigate whether this observation could be explained by the production of fermentation products induced by malabsorbed carbohydrate in the colon, or by stimulating the incretin glucagon-like peptide 1 (7-36) amide that is released from the large bowel. We used lactulose as a model for resistant starch carbohydrate. Ten insulin-resistant male volunteers, who had undergone previous coronary artery bypass grafting, volunteered to take part in the study and underwent 6 d of lactulose loading (15 g/d for 2 d and 30 g/d for 4 d). There was no significant change in insulin, glucose, free fatty acids, or glucagon-like peptide 1 (7-36) amide response to an oral glucose tolerance test following the lactulose despite a significant rise in breath hydrogen. Large bowel fermentation stimulated by lactulose appears to have no significant effect on insulin, glucose, free fatty acids, and glucagon-like peptide 1 (7-36) response in patients with coronary heart disease.     

Intensification of therapy and no increase in body mass index with longer disease duration in type 2 diabetes mellitus (ZODIAC-5)

BACKGROUND: Decreased insulin sensitivity and beta-cell failure are the two key components in the pathogenesis of type 2 diabetes mellitus (T2DM). Secondary treatment failure is often attributed to the development of obesity-related insulin resistance in combination with continued loss of beta-cell function. OBJECTIVE: Assess metabolic control, body mass index (BMI) and treatment in relationship to diabetes duration to study these mechanisms. METHODS: Cross-sectional study of 7875 patients with T2DM in primary care in The Netherlands. Clinical data and laboratory results were obtained for the 2005 annual visit. Patients were grouped according to diabetes duration in 2-year intervals. Each step in the traditional treatment sequence was considered as a sign of progression of beta-cell failure. RESULTS: Complete data regarding duration and treatment were available for 6850 patients (87%). After the initial years following diagnosis, treatment with diet alone decreases and oral hypoglycaemic agents (OHA) are prescribed to an increasing percentage of patients. Treatment with OHA diminishes after approximately 10 years following diagnosis and treatment with insulin increases until approximately two-thirds of patients with diabetes duration of more than 20 years are being treated with insulin. BMI does not increase with longer disease duration. CONCLUSION: The concept of beta-cell failure as the primary determinant of the chronic progression of T2DM is supported by these results, whereas a deterioration of obesity-related insulin sensitivity as indicator is not supported.     

Lipoprotein(a): an independent risk factor for ischemic heart disease that is dependent on triglycerides in subjects with type 2 diabetes mellitus

   

Lipoprotein(a) is an independent risk factor for Ischaemic Heart Disease (IHD) in the general population. There are conflicting reports in the extent of its association with IHD among subjects with Type 2 diabetes mellitus (T2DM).     

A cross-sectional analysis of type II diabetes in a community with exposure to perfluorooctanoic acid (PFOA)

Background

Increased diabetes mortality has been reported in workers exposed to perfluorooctanoic acid (PFOA). We analyzed the relationships among serum PFOA, type II diabetes, and fasting glucose in a population with high levels of serum PFOA resulting from drinking contaminated water.

Methods

The study population was adults participating in a health survey in 2005-2006 (N=54,468). Subjects reported prevalent diabetes, age at diagnosis, and provided blood in which serum PFOA and glucose levels were measured. We conducted a case-control analysis restricted to long-time residents (≥20 years, N=13,922), to maximize the likelihood that serum PFOA levels in 2005 reflected previous exposure. Cases (N=1055) were restricted to those with medical record validation and at least 10-year residence prior to diagnosis. We also studied fasting glucose and serum PFOA in a subset (N=21,642).

Results

Median serum PFOA was 28 ng/ml, compared with 4 ng/ml in the general US population. Reported diabetes prevalence was 7.8%, similar to what was expected. Adjusted for confounders, all upper deciles of serum PFOA had a decreased risk of diabetes compared with the lowest (odds ratios—ORs by decile, 1.00, 0.71, 0.60, 0.72, 0.65, 0.65, 0.87, 0.58, 0.62, 0.72). There was no consistent pattern between fasting serum glucose and PFOA (glucose by decile, 94, 95, 95, 93, 94, 92, 92, 92, 92, 93, adjusted for confounders).

Conclusions

Our findings do not demonstrate an association between PFOA and either type II diabetes or fasting glucose level. Our data are limited by their cross-sectional nature, and do not preclude the possibility of a causal relationship.     

Association of individual and area-level socioeconomic conditions with quality of life and glycaemic control in 11- to 21-year-old adolescents with early-onset type 1 diabetes: a cross-sectional study

Purpose

To analyse the association of area-level deprivation (German Index of Multiple Deprivation, GIMD 2010) with health- and disease-related quality of life (QoL) and glycaemic control (HbA1c) jointly with individual-level socioeconomic status (SES) in young patients with preschool-onset type 1 diabetes.

Methods

A total of 425 male and 414 female patients aged 11–21 years from a Germany-wide population-based survey completed the generic KINDL-R, the DISABKIDS chronic-generic module (DCGM-12), and the DISABKIDS diabetes-specific module with impact and treatment scales (QoL indicators; range 0–100 with higher scores representing better QoL). To analyse the association of area-level deprivation and SES with QoL and HbA1c, multiple linear regression models were applied adjusting for sociodemographic and health-related variables.

Results

Mean QoL scores (SD) were 73.2 (12.2) for the KINDL-R, 76.1 (16.1) for the DCGM-12, 66.2 (19.9) for diabetes impact, and 56.4 (27.3) for diabetes treatment (DISABKIDS). Mean HbA1c was 8.3 (1.4)%. While both QoL outcomes and HbA1c level improved with increasing individual SES, no association was observed between area-level deprivation (GIMD 2010) and either outcome.

Conclusions

Compared with individual SES, area-level deprivation seems to be of minor importance for QoL and glycaemic control in young people with early-onset type 1 diabetes.

     

Change in health status (EQ-5D) over 5 years among individuals with and without type 2 diabetes mellitus in the SHIELD longitudinal study

ABSTRACT: BACKGROUND: Health-related quality of life studies among adults with type 2 diabetes mellitus, using the EQ-5D, have been short term and have not assessed change over years. This study assessed the change in health status and health-related quality of life over 5 years among individuals with and without diabetes. METHODS: Respondents to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) completed the EuroQol-5D (EQ-5D) at baseline (2004) and 5 years later (2009). Visual analog scale (VAS) score and health index score were computed at baseline and year 5, and the change over 5 years was measured for individuals with type 2 diabetes mellitus (T2DM) and those without diabetes, and T2DM adults with and without diabetic complications. Linear regression models were used to determine change in EQ-5D score, controlling for age, gender, race, education, household income, and body mass index (BMI). RESULTS: There was significantly greater decline in the EQ-5D index score in the T2DM group (-0.031 [SD 0.158]), compared with those without diabetes (-0.016 [0.141], p = 0.001). Compared with respondents without diabetes, those with T2DM had a larger reduction in EQ-5D index score, after controlling for demographics (p = 0.001). EQ-5D VAS score declined over 5 years for both groups: -1.42 (18.1) for the T2DM group, and -0.63 (15.8) for the group without diabetes, but the between-group difference was not significant either before (p = 0.09) or after (p = 0.12), controlling for demographics. T2DM respondents with diabetic complications had a greater decline in EQ-5D scores than T2DM respondents without complications (p < 0.05). CONCLUSION: Over a 5-year period, health status of respondents with T2DM declined significantly compared with those with no diabetes, indicating that the burden of the disease has a long-term detrimental impact. This decline in health status is likely to impact utility scores (fewer quality-adjusted life years) for economic evaluations.     

Effects of dietary fiber and insulin treatment on serum levels of lipids and lipoprotein (a) in patients with type II diabetes mellitus]

OBJECTIVE. As lipoprotein(a) is an independent risk factor for the development of coronary heart disease we determined the effect on serum lipid and lipoprotein(a) levels of dietary fibre and of treatment with insulin in patients with diabetes mellitus type II. METHODS. Twelve type II diabetic patients (mean age 62 (SD 10) yrs, body mass index 25.8 (SD 3.5) kg/m2), all treated with oral antidiabetic agents, were studied in a randomised cross-over trial, in which they used breads meals prepared with guar gum (a mean of 11.2 g guar per day) for 3 months in comparison with normal high-fibre bread. Fifteen other patients (age 70 (8), BMI 27.4 (5.6) kg/m2) poorly controlled on oral hypoglycaemic agents, were treated with insulin. RESULTS. The guar treatment of the 12 patients resulted in lower total cholesterol (5.24 vs 5.7 mmol/l, p less than 0.1) and LDL cholesterol (3.77 vs 4.33 mmol/l, p less than 0.001) in comparison with normal high-fibre bread. Lipoprotein(a) levels were not different (76 vs 82 mg/l). Insulin therapy in the 15 other patients decreased HbA1c levels after 6 months from 11.0 to 7.7% (p less than 0.001), total cholesterol from 6.8 to 6.1 mmol/l (p less than 0.05), and LDL cholesterol from 4.4 to 4.1 mmol/l (p less than 0.05). Lp(a) decreased only slightly in 11/15 patients, from 491 to 441 mg/l (p = 0.07). CONCLUSION. Neither the use of the dietary fibre guar nor improved metabolic control with insulin therapy lowered elevated lipoprotein(a) levels in type II diabetic patients.     

From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I diabetes mellitus with optic atrophy (Wolfram syndrome)

Wolfram syndrome patients are mainly characterised by juvenile onset diabetes mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural high-frequency hearing impairment are important additional features. This rare autosomal recessively inherited neurodegenerative syndrome is caused by mainly inactivating mutations in the WFS1 gene. It is located at chromosome 4p16 and encodes wolframin, a transmembrane protein. No function has yet been ascribed to this protein.     

The conjugated linoleic acid (CLA) isomer,t10c12-CLA,is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.     

Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice

Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β cells leads to impaired glucose metabolism and its attendant complications. IA2(5)P2-1, a potent immunogenic carrier which designed by our laboratory, can induce high titer specific antibodies when carry a B cell epitope, such as B cell epitopes of DPP4, xanthine oxidase, and Urate transporter protein. In this report, we describe a novel multi-epitope vaccine composing a peptide of DPP4, an anti-diabetic B epitope of Insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in non-obese diabetic (NOD) mice successfully induced specific anti-DPP4 antibody, inhibited plasma DPP4 activity, and increased serum GLP-1 level. Moreover, this antibody titer was correlated with the dose of immunization (20μg, 100μg). Inoculation of this vaccine in NOD mice significantly control blood glucose level, improved glucose excursion and increased insulin level in vivo. Consistent with a lower diabetic and insulitis incidence, a induced splenic T cells proliferation and tolerance were observed. IFN-γ secretion reduced and IL-10 increased significantly in the D41-IA2(5)-P2-1 treated mice compared to P277 and control group due to the potential immunomodulatory effect of the epitope in the vaccine. Immunohistochemical analysis and cytometry showed a rebalance of Th1/Th2 in NOD mice. Our results demonstrate that this multi-epitope vaccine may serve as a promising therapeutic approach for type 1 diabetes.     

Adjuvant effect of Japanese herbal medicines on the mucosal type 1 immune responses to human papillomavirus (HPV) E7 in mice immunized orally with Lactobacillus-based therapeutic HPV vaccine in a synergistic manner

The Japanese herbal medicines, Juzen-taiho-to (JTT) and Hochu-ekki-to (HET), have been shown to enhance humoral immune responses to vaccine antigen when used as adjuvants for prophylactic vaccines. However, their adjuvant effect on mucosal cellular immune responses remains unstudied. The precursor lesion of cervical cancer, high-grade CIN that expresses HPV E7 oncoprotein ubiquitously is a target for HPV therapeutic vaccines that elicit mucosal E7-specific type 1 T cell responses. We have demonstrated that oral immunization with recombinant Lactobacillus casei expressing HPV16 E7 (LacE7) is more effective in eliciting mucosal E7-specific IFNγ-producing cells than subcutaneous or intramuscular antigen delivery. Here we report the synergistic effect of an oral Lactobacillus-based vaccine and Japanese herbal medicines on mucosal immune responses. Oral immunization of mice with LacE7 plus either a Japanese herbal medicine (JTT or HET) or a mucosal adjuvant, heated-labile enterotoxin T subunit (LTB), promotes systemic E7-specific type 1 T cell responses but not mucosal responses. Administration of LacE7 plus either Japanese herbal medicine and LTB enhanced mucosal E7-specific type 1 T cell response to levels approximately 3-fold higher than those after administration of LacE7 alone. Furthermore, secretion of IFNγ and IL-2 into the intestinal lumen was observed after oral administration of LacE7 and was enhanced considerably by the addition of Japanese herbal medicines and LTB. Our data indicated that Japanese herbal medicines, in synergy with Lactobacillus and LTB, enhance the mucosal type 1 immune responses to orally immunized antigen. Japanese herbal medicines may be excellent adjuvants for oral Lactobacillus-based vaccines and oral immunization of LacE7, HET and LTB may have the potential to elicit extremely high E7-specific mucosal cytotoxic immune response to HPV-associated neoplastic lesions.