There is considerable interest in dietary and other approaches to maintaining blood glucose concentrations within the normal range and minimizing exposure to postprandial hyperglycemic excursions. The accepted marker to evaluate the sustained maintenance of normal blood glucose concentrations is glycated hemoglobin A1c (HbA1c). However, although this is used in clinical practice to monitor glycemic control in patients with diabetes, it has a number of drawbacks as a marker of efficacy of dietary interventions that might beneficially affect glycemic control in people without diabetes. Other markers that reflect shorter-term glycemic exposures have been studied and proposed, but consensus on the use and relevance of these markers is lacking. We have carried out a systematic search for studies that have tested the responsiveness of 6 possible alternatives to HbA1c as markers of sustained variation in glycemic exposures and thus their potential applicability for use in dietary intervention trials in subjects without diabetes: 1,5-anhydroglucitol (1,5-AG), dicarbonyl stress, fructosamine, glycated albumin (GA), advanced glycated end products (AGEs), and metabolomic profiles. The results suggest that GA may be the most promising for this purpose, but values may be confounded by effects of fat mass. 1,5-AG and fructosamine are probably not sensitive enough to the range of variation in glycemic exposures observed in healthy individuals. Use of measures based on dicarbonyls, AGEs, or metabolomic profiles would require further research into possible specific molecular species of interest. At present, none of the markers considered here is sufficiently validated and sensitive for routine use in substantiating the effects of sustained variation in dietary glycemic exposures in people without diabetes.

Purpose: The aims of this study were to analyze the prevalence and course of disordered eating behavior (DEB) in adolescents with intensively treated type I diabetes, describe differences in age-specific DEB symptoms, and identify predictors of current DEB. Methods: Data were taken from 332/218 11- to 27-year-old participants (55.7% girls/women, mean age [SD] 17.8 [3.4] years, mean diabetes duration 14.9 [3.0] years) of two/three surveys of a Germany-wide longitudinal study on early-onset and long duration diabetes, respectively. A diabetes-adapted version of the SCOFF questionnaire was used to assess DEB. Both screening-based overall and age- and sex-specific prevalence of DEB and its symptoms were determined. To estimate transition probabilities between DEB states, first-order Markov transition models were implemented adjusting for previous sociodemographic, socioeconomic, and diabetes-specific covariates. Results: The overall screening-based DEB prevalence among all 1,318 observations was 10.8% (95% confidence interval [CI]: 9.2%, 12.6%) with age-specific differences in symptom prevalence. Transition probabilities for developing/persistent DEB were twofold higher among female than male participants (risk ratio [RR] 2.3 [1.4, 3.9]/2.1 [1.3, 3.4]). In multiple adjusted regression, previous DEB (odds ratio [OR] 2.8 [95% CI 1.4, 5.6]), follow-up time (ORper 1-year increase 3.4 [1.4, 8.0]), and sex (ORgirls/(women) 2.1 [1.1, 3.9]) were the most important predictors of current DEB with further weaker associations for previous age and HbA(1c). Conclusions: Our results contribute to better understanding the course of DEB in patients with early-onset diabetes and emphasize the relevance of regular DEB screenings including the age group of young adults. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.

Given the short-comings of randomized controlled trials, such as low numbers of patients and events, we aimed to perform a network meta-analysis of observational trials on the effects of non-insulin glucose-lowering drugs on all-cause and cardiovascular mortality in type 2 diabetes. We searched MEDLINE and EMBASE through August 2017. From the 38 eligible studies, we extracted patient characteristics, exposure, outcome, confounder-adjusted effect measures, and risk of bias. All-cause and cardiovascular mortality risk were assessed with random-effects network meta-analysis. In 32 studies reporting on all-cause mortality (1,661,945 persons) and in 11 studies on cardiovascular mortality (358,784 persons), 119,591 (7.2%) and 9,221 (2.6%) persons, respectively, died during follow-up. Compared to metformin, sulfonylurea drugs (SU) increased all-cause mortality risk (HR: 1.42 (95% CI: 1.29-1.56)). Dipeptidyl peptidase-4 inhibitors (DDP4i) added to metformin significantly decreased all-cause mortality risk compared to metformin monotherapy (HR: 0.76 (0.63-0.93)), any other drug class as monotherapy, and SU + metformin dual therapy (HR: 0.69 (0.60-0.79)). DPP-4i + metformin dual therapy was associated with even larger reductions in risk of cardiovascular mortality; HR: 0.40 (0.21-0.79) when compared to metformin monotherapy, and HR: 0.41 (0.23-0.74) when compared to SU + metformin dual therapy. Glucagon-like-peptide-1 receptor agonists + metformin dual therapy tended to, but did not significantly, decrease mortality risk when compared to metformin monotherapy (all-cause mortality, HR: 0.88 (0.53-1.47); cardiovascular mortality, HR: 0.74 (0.30-1.82)). In conclusion, this large network meta-analysis evidently confirmed that SU, compared to metformin, increased all-cause mortality risk. DPP-4i + metformin dual therapy, compared to other treatments, resulted in a consistent risk reduction of both all-cause and cardiovascular mortality. Disclosure B. Bongaerts: None. L.M. Lindner: None. A. Hoyer: None. O. Kuss: None. C. Herder: Other Relationship; Self; Sanofi, Eli Lilly and Company. H. Al-Hasani: None. K. Müssig: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. W. Rathmann: Advisory Panel; Self; AstraZeneca. Research Support; Self; Novo Nordisk A/S.

AimThe aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus. MethodsOvid MEDLINE was searched to identify relevant cohort, case-control or cross-sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle-Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement. ResultsLiterature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle-Ottawa Scale, most of the studies were of average quality. Results on associations of socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio-economic status and higher area-level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study. ConclusionsLower socio-economic status and higher area-level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities. What's new? This is the first systematic review to investigate the association of individual-level as well as area-level socio-economic status and area-level deprivation with short-term healthcare outcomes in Type 1 diabetes mellitus. Short-term healthcare outcomes included glycaemic control, hypoglycaemia and diabetic ketoacidosis. Associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia in youth and adults were heterogeneous between studies. Lower individual-level as well as lower area-level socio-economic status and higher area-level deprivation were associated with an increased risk of diabetic ketoacidosis at all ages.

OBJECTIVES:To describe incidence rates and temporal trends of severe hypoglycemia (SH) and of hospitalizations for SH or diabetic ketoacidosis (DKA) in persons with early-onset, long-term type 1 diabetes (T1D) and associations of these short-term complications with potential risk factors. METHODS:This study includes data of 1,875 persons 11.2 to 21.9 years of age with early-onset (<5 years) and long-term (>10 years) T1D from 3 cross-sectional nationwide, population-based surveys conducted in 2009/2010, 2012/2013 and 2015/2016 using standardized questionnaires. Negative binomial regression was used to estimate incidence rates per 100 person-years (py), temporal trends and associations between potential risk factors and outcomes. RESULTS:The crude incidence rate of SH showed a decreasing trend over time (P for trend = .004), disappearing after adjustment for confounders (P for trend = .341). In contrast, adjusted rates of SH- and DKA-associated hospitalizations did not change significantly between 2009 and 2016 (P for trend = .306 and .774, respectively). Associations between sex, diabetes duration, insulin treatment regimen, hypoglycemia awareness as well as physical activity and SH were found, while family structure was associated with hospitalizations for SH. Family structure, socioeconomic status (SES), diabetes duration, and hemoglobin A1c values showed associations with DKA-related hospitalizations. CONCLUSIONS:After adjustment, rates of SH and SH- or DKA-associated hospitalization showed no significant changes in recent years. Structured education programs focusing on high-risk groups as, for example, persons with T1D living with 1 biological parent and the parents' partner or those with a low SES, should be implemented to reduce incidence rates of hospitalizations.

Aims. To estimate the risk of microvascular complications and macrovascular risk factors among persons with early-onset (diagnosed at ages 0 to <5 years) and long-duration type 1 diabetes and determine temporal trends and associations with potential predictors. Methods. We conducted three population-based cross-sectional surveys in Germany (N=1789) to obtain information on exposures and five outcomes (retinopathy, nephropathy, dyslipidemia, hypertension, and a composite endpoint combining all four outcomes). For each outcome, log-binomial spline regression was applied to estimate the risk and dose-response relationship with diabetes duration and exposures. Results. The risk for microvascular complications increased after 14 years since diabetes diagnosis whereas dyslipidemia and hypertension were already prevalent at 10 years. The 15-year risk (95% confidence interval) of the composite endpoint for female and male patients was 22.9% (18.8%–27.9%) and 19.2% (15.5%–23.8%), respectively. Temporal trends suggested a decreasing risk between 2009 and 2016. Glycemic control, lifestyle-related factors, and SES, but not health care-related factors, were associated with the risk of the composite endpoint. Conclusions. In early-onset type 1 diabetes, there exists a considerable risk of complications and comorbidities already in young ages. Future research should focus on prevention of diabetic complications in young patients and clarification of pathways of the associations found.