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This retrospective chart review study evaluated the effectiveness of the FreeStyle Libre Flash Glucose Monitoring SystemTM when used by adults with type 2 diabetes (T2DM) as their standard of care in a real-world setting. This study aimed to determine the effect of FreeStyle Libre when used for between 3 months to 6 months on HbA1c. The study population included adults on a basal-bolus insulin regimen for at least 1 year who had been using FreeStyle Libre regularly for at least 3 months (either self-funded or prescribed) and with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol). Pregnant patients were excluded, as were patients on dialysis. A total of 92 records from insulin using patients with T2DM from 6 hospital sites in Austria were included in this chart review. On average, HbA1c was 8.8±0.8% (72.2±8.9 mmol/mol), prior to FreeStyle Libre use, age was 64.4±9.7 years, BMI was 30.8±5.5 kg/m2 and average duration of insulin use 7.6±5.6 years (mean±SD), 79.3% of patients were on oral antidiabetic medications (metformin, TZD, DPP-4 or SGLT) and 54.3% were male. CVD and renal complications were reported by 34.8% and 27.2% of patients, respectively. HbA1c results were recorded between 91 to 194 days from the start of use of FreeStyle Libre, between September 2014 and July 2018. To minimise selection bias, all patients that had used FreeStyle Libre for at least 3 months from each study site were included in the analysis. After at least 3 months of using FreeStyle Libre, HbA1c (primary outcome) was significantly reduced by 0.9±0.8% (mean±SD); p Disclosure P. Fasching: None. H. Brath: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk Inc., Servier. Speaker’s Bureau; Self; Amgen Inc., Ascensia Diabetes Care, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk Inc., Pfizer Inc., Sanofi. C. Ebenbichler: None. J.K. Mader: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Prediktor Medical, Roche Diabetes Care, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; decide Clinical Software GmbH. C. Schelkshorn: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. Speaker’s Bureau; Self; Abbott, Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Self; Lilly Diabetes. R. Weitgasser: Research Support; Self; Abbott.

Background and Aims: Apolipoprotein C3 (ApoC3) is a key regulator of triglyceride metabolism via its inhibitory effects on lipolysis and hepatic remnant uptake. Emerging evidence indicate that ApoC3 is an independent risk factor for cardiovascular events. The fact that glucose and insulin regulates ApoC3 expression raises the role of ApoC3 and cardiovascular risk in diabetes. We, therefore, investigated ApoC3 and its association with cardiovascular disease (CVD) in patients with and without diabetic nephropathy. Methods: This cross-sectional and prospective analysis was part of the prospective, ongoing Finnish Diabetic Nephropathy (FinnDiane) Study. Between 1994 and 2015 data were obtained from 3926 type 1 diabetes (T1D) patients at more than 80 hospitals or health centers across Finland. ApoC3 levels were explored by groups of albuminuria, CKD stages, presence of CVD as well as prediction of CVD and death. Survival curves were calculated by Cox regression analysis. Results: At baseline, normo-, micro- and macroalbuminuria were present in 71.7%, 13.8% and 14.5% of the population (n=3926, females 48%, age 37.8±12.2 years, diabetes duration 23.2±13 years, HbA1c 8.4±1.5%). CKD stage 3-5 was diagnosed in 14.3%. Coronary heart disease or stroke (CVD) were present in 5.5% at baseline, while 16.3% developed CVD during 15-year follow-up. Compared to normoalbuminuria ApoC3 was elevated in the presence of micro- (p=0.013) or macroalbumiuria (p Conclusions: Baseline ApoC3 levels were elevated in T1D patients with micro- and macroalbuminuria, with impaired renal function, and with CVD. ApoC3 also predicted the development of CVD and death during follow-up. Disclosure L. Stechemesser: None. C. Forsblom: None. R. Weitgasser: None. P. Groop: Other Relationship; Self; AstraZeneca, AbbVie Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medscape, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi.

Peroxisome proliferator–activated receptor coactivator-1α (PGC-1α) is a transcriptional coactivator implicated in transcriptional programs of hepatic gluconeogenesis, oxidative phosphorylation, and insulin release by β-cells. To study associations of the PGC-1α gene locus with carbohydrate metabolism and type 2 diabetes in humans, we identified several polymorphisms in the promoter region that were located in a haplotype block distinct from a second haplotype block containing part of intron 2 and extending beyond exon 13. Each block contained five common haplotypes. Oral glucose tolerance testing revealed associations of promoter haplotype combinations with 30- and 60-min postload plasma glucose levels, whereas haplotypes in both blocks were associated with indexes of β-cell function. The associations of promoter haplotypes are supported by functional studies showing that some polymorphisms are located in transcription factor binding sites and affect transactivation in an allele-specific manner. By comparing patients with type 2 diabetes and control subjects, we observed borderline significant differences of four-loci haplotype distributions in the downstream haplotype block. Moreover, the haplotype that was associated with the strongest insulin response to glucose conferred the lowest risk of type 2 diabetes (P < 0.01). Thus, the PGC-1α gene locus influences carbohydrate metabolism and contributes to type 2 diabetes in the population studied.

Obesity is frequently associated with type 2 diabetes. We previously observed an association of a functional G/A polymorphism in the uncoupling protein 2 (UCP2) promoter with obesity. The wild-type G allele was associated with reduced adipose tissue mRNA expression in vivo, reduced transcriptional activity in vitro, and increased risk of obesity. On the other hand, studies in animal and cell culture models identified pancreatic β-cell UCP2 expression as a main determinant of the insulin secretory response to glucose. We therefore ascertained associations of the −866G/A polymorphism with β-cell function and diabetes risk in obesity. We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the β-cell line INS1-E. By studying 39 obese nondiabetic humans, we observed genotype differences in β-cell function; wild-type subjects displayed a greater disposition index (the product of insulin sensitivity and acute insulin response to glucose) than subjects with the variant allele (P < 0.03). By comparing obese subjects with and without type 2 diabetes, we observed genotype-associated differences in diabetes prevalence that translated into a twofold age-adjusted risk reduction in wild-type subjects. Thus, the more common UCP2 promoter G allele, while being conducive for obesity, affords relative protection against type 2 diabetes.