Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration: The Joslin 50-Year Medalist Study

Objective: To assess complication prevalence and identify protective factors in patients with diabetes duration of $\geq$50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. Research Design and Methods: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for $\geq$50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA$_{1c}$, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. Results: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. Conclusions: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy

Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects : a randomised double-blind placebo-controlled cross-over study

Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.Peer reviewe

Care of vision and ocular health in diabetic members of a national diabetes organization: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Regular examination and early treatment of diabetic retinopathy can prevent visual loss. The aim of the study was to describe the care of vision and ocular health in people with diabetes in Norway.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey of a random sample (n = 1,887) of the Norwegian Diabetic Associations' (NDA) members was carried out in 2005. Questions were asked about care of vision and ocular health, history of ocular disease and visual symptoms, general medical history and diabetes management. The study was approved by the Regional Committee for Medical Research Ethics.</p> <p>Results</p> <p>The response rate was 74%. Forty-four questionnaires with incomplete data regarding gender, age or type of diabetes were excluded, leaving 1352 cases (52% females) for analysis. 451 (33%) had type 1 and 901 (67%) had type 2 diabetes, the mean duration of diabetes was respectively, 22 (sd ± 14) and 10 (sd ± 9) years. In all 1,052 (78%) had their eyes examined according to guidelines and 1,169 (87%) confirmed to have received information about regular eye examinations. One in two recalled to have received such information from their general practitioner. To have received information about the importance of eye examinations (PR 3.1, 95% CI 2.4 to 4.0), and diabetes duration > 10 years (PR 1.2, 95% CI 1.2 to 1.3), were independently associated with reporting regular eye examinations. A history of diabetic retinopathy was reported by 178 (13%) responders, of which 101 (57%) reported a history of laser treatment. Responders who had regular eye examinations reported more frequently a history of diabetic retinopathy (19% vs. 5%, p < 0.001). The frequency of retinopathy was significantly higher in responders with reported HbA1c values above treatment target (23% vs. 13%, p = 0.001). However, in responders who were not regularly examined, there was no difference in reported frequency of retinopathy with regard to HbA1c level.</p> <p>Conclusion</p> <p>Eight out of ten diabetic members of the NDA had their eyes examined according to current guidelines and the majority was well informed about the risk of vision loss due to diabetes. The results indicate that the reported history of diabetic retinopathy likely underestimates the prevalence of retinopathy.</p

The Impact of Oral Health on Taste Ability in Acutely Hospitalized Elderly

Objective: To investigate to what extent various oral health variables are associated with taste ability in acutely hospitalized elderly. Background: Impaired taste may contribute to weight loss in elderly. Many frail elderly have poor oral health characterized by caries, poor oral hygiene, and dry mouth. However, the possible influence of such factors on taste ability in acutely hospitalized elderly has not been investigated. Materials and Methods: The study was cross-sectional. A total of 174 (55 men) acutely hospitalized elderly, coming from their own homes and with adequate cognitive function, were included. Dental status, decayed teeth, oral bacteria, oral hygiene, dry mouth and tongue changes were recorded. Growth of oral bacteria was assessed with CRTH Bacteria Kit. Taste ability was evaluated with 16 taste strips impregnated with sweet, sour, salty and bitter taste solutions in 4 concentrations each. Correct identification was given score 1, and maximum total taste score was 16. Results: Mean age was 84 yrs. (range 70–103 yrs.). Total taste score was significantly and markedly reduced in patients with decayed teeth, poor oral hygiene, high growth of oral bacteria and dry mouth. Sweet and salty taste were particularly impaired in patients with dry mouth. Sour taste was impaired in patients with high growth of oral bacteria. Conclusion: This study shows that taste ability was reduced in acutely hospitalized elderly with caries activity, high growt

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Mortality in diabetic patients participating in an ophthalmological control and screening programme

The aim of this follow-up study has been to assess retinopathy and change of treatment to insulin therapy as risk factors for mortality in diabetic patients participating in a control and screening programme for retinopathy. A total of 3220 diabetic patients, 483 with an age at diagnosis <30 years, and 2737 with an age at diagnosis ≤30 years, were included. Retinopathy was graded on fundus photographs using the Wisconsin Scale, and the visual acuity was assessed. The average HbA(1c) value was calculated for each patient for the previous 8 years to estimate long-term glycaemic control. Mortality data were obtained from death certificates. Two hundred and sixty-three diabetic patients (8.2 %) died during the mean follow-up time of 3.4 years, 13 (2.7 %) of those with younger-onset (<30 years) and 250 (9.1%) of those with older-onset (≤30 years) diabetes. Of them, 148 (56.3 %) died from cardiovascular and 23 (8.7 %) from cerebrovascular disorders. After adjusting for differences in age and sex, more severe retinopathy and the use of antihypertensive drugs were associated with a decreased overall survival rate as well as an increased mortality from cardiovascular and cerebrovascular diseases. A statistically significant association between HbA(tc) values in the highest quartile, i.e. ≤8.4 %, and cardiovascular and all cause mortality did not remain when retinopathy was entered into the multivariate analyses. Duration of diabetes, but not change of treatment to insulin therapy, was associated with higher cardiovascular mortality in patients whose diabetes was diagnosed after the age of 30 years. We conclude that severe retinopathy, use of antihypertensive drugs, and poor glycaemic control predicted death from cardiovascular disease in diabetic patients participating in an ophthalmological screening programme