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  • 1
    Online Resource
    Online Resource
    Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment
    American Diabetes Association ; 2021
    In:  Diabetes Care Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227
    Abstract: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P & lt; 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc20-2842
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
    detail.hit.zdb_id: 1490520-6
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  • 2
    Online Resource
    Online Resource
    Irreversibility of the Defect in Glycogen Synthase Activity in Skeletal Muscle From Obese Patients With NIDDM Treated With Diet and Metformin
    American Diabetes Association ; 1998
    In:  Diabetes Care Vol. 21, No. 9 ( 1998-09-01), p. 1489-1494
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 21, No. 9 ( 1998-09-01), p. 1489-1494
    Abstract: To assess the reversibility of the defect in glycogen synthase (GS) activity in skeletal muscle from obese patients with NIDDM treated with a hypocaloric diet and metformin. RESEARCH DESIGN AND METHODS Eighteen obese patients newly diagnosed with NIDDM were included in a randomized placebo-controlled double-blind parallel group trial and followed for 3 months. Euglycemic-hyperinsulinemic clamp including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus metformin or placebo. The patients were studied at basal, low, and high insulin concentrations. RESULTS The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia (for 8 h) or by chronic reduction of hyperglycemia by diet plus metformin. In both treatment groups, comparable effects on glycemic control and weight loss were found together with marked insulin suppression of nonesterified fatty acids and increased glucose oxidation. Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25% at high insulin level (259 ± 31 vs. 207 ± 21 mg · m−2 · min−1, P & lt; 0.05). An insignificant increase by 13% was found in the placebo group. There were no significant changes in nonoxidative glucose metabolism. GS activity and glucose utilization showed no significant differences between the two treatment groups when regression coefficients, expressed as incremental changes by increments of insulin, were compared. CONCLUSIONS Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia. Metformin and diet had no significant influence on GS activity. The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.21.9.1489
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1998
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  • 3
    Online Resource
    Online Resource
    Studies of Association of Variants Near the HHEX , CDKN2A/B , and IGF2BP2 Genes With Type 2 Diabetes and Impaired Insulin Release in 10,705 Danish Subjects
    American Diabetes Association ; 2007
    In:  Diabetes Vol. 56, No. 12 ( 2007-12-01), p. 3105-3111
    Details
    In: Diabetes, American Diabetes Association, Vol. 56, No. 12 ( 2007-12-01), p. 3105-3111
    Abstract: OBJECTIVE— In the present study, we aimed to validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) loci, as well as the intergenic rs9300039 variant. Furthermore, we aimed to characterize quantitative metabolic risk phenotypes of the four variants. RESEARCH DESIGN AND METHODS— The variants were genotyped in the population-based Inter99 cohort (n = 5,970), the ADDITION Study (n = 1,626), a population-based sample of young healthy subjects (n = 377), and in additional type 2 diabetic case (n = 2,111) and glucose-tolerant (n = 521) subjects. The case-control studies involved a total of 4,089 type 2 diabetic patients and 5,043 glucose-tolerant control subjects. RESULTS— We validated association of variants near HHEX/KIF11/IDE, CDKN2A/B, and IGF2BP2 with type 2 diabetes. Interestingly, in middle-aged people, the rs1111875 C-allele of HHEX/KIF11/IDE strongly associated with lower acute insulin response during an oral glucose tolerance test (P = 6 × 10−7). In addition, decreased insulin release following intravenous tolbutamide injection was observed in young healthy subjects (P = 0.02). Also, a reduced insulin release was observed for the CDKN2A/B rs10811661 T-allele after both oral and intravenous glucose challenges (P = 0.001 and P = 0.009, respectively). CONCLUSIONS— We validate that variants in the proximity of the HHEX/KIF11/IDE, CDKN2A/B, and IFG2BP2 loci associate with type 2 diabetes. Importantly, variations within the HHEX/KIF11/IDE and CDKN2A/B loci confer impaired glucose- and tolbutamide-induced insulin release in middle-aged and young healthy subjects, suggesting a role for these variants in the pathogenesis of pancreatic β-cell dysfunction.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db07-0856
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2007
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  • 4
    Online Resource
    Online Resource
    797-P: Usability and Satisfaction of a New Affordable Insulin Pen for All: Positive Outcomes of Two Usability Studies
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Globally, 13 million people (4 million in USA) inject insulin with single use disposable syringes daily. Compared to syringe and vials, pens are known to increase adherence and diabetes control and to reduce healthcare utilization costs. Yet, pens are largely unavailable to low-income groups, due to prohibitive cost. GO-Pen has designed a new affordable pen for use with vial insulin and conducted usability testing in collaboration with Médecins Sans Frontières (MSF) , an international medical humanitarian organization working to improve diabetes care for people living in difficult circumstances. Here we report the results of two usability studies conducted among insulin pen users (n=19, f/m: 11/8, age: 23-64) and syringe users (n=20, f/m: 10/10, age: 24-70) in refugee populations in Malaysia and Jordan. A convenience sample of the first 20 to accept enrollment was set up after informed consent. After a short introduction, participants were asked to demonstrate the use of the insulin pen in front of a camera, without revealing their faces or any identifying information, while an interviewer noted their correct use and confidence level. Injection was simulated in a sponge. 100% (n=19) of pen users and 75% (n=15) of syringe users performed & gt;90% of the tasks correctly. Among pen users, the most common failed tasks were priming the needle (n=4) . Among syringe users, the most common failed tasks were failing to check the vial label (n=9) and priming the needle (n=6) . 5% (n=1) of pen users preferred the new insulin pen over the pen they were already familiar with. 75% (n=15) of syringe users preferred the new insulin pen over syringes. The most common complaint among pen users was that there were too many steps in the process. In conclusion, we find current pen users require little training and prefer the pen they are already familiar with. Syringe users who are unfamiliar with pen usage require more training than pen users, however, they have largely favorable attitudes towards this new insulin pen. Disclosure O.K.Nielsen: Stock/Shareholder; GO-Pen ApS. G.Huisman: None. J.A.Qasem: None. C.Eng: None. A.F.Jørgensen: None. M.Torrone: None. B.S.Larsen: None. A.Reddy: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-797-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
    American Diabetes Association ; 2017
    In:  Diabetes Care Vol. 40, No. 1 ( 2017-01-01), p. 117-124
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 40, No. 1 ( 2017-01-01), p. 117-124
    Abstract: Reduced heart rate variability (HRV) and increased heart rate (HR) have been associated with cardiovascular mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) increase HR, and studies have suggested that they may reduce HRV. We examined the effect of the GLP-1 RA liraglutide on HRV and diurnal variation of HR in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD). RESEARCH DESIGN AND METHODS Liraglutide or placebo was administrated to a backbone therapy of metformin in this double-blind, placebo-controlled 12 + 12–week crossover study. SD of beat-to-beat (NN) intervals (SDNN) was assessed by 24-h Holter monitoring as a measure of HRV. Diurnal HR variation and sympathovagal balance analyzed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF) and low-frequency (LF) power were assessed. RESULTS Compared with placebo, liraglutide decreased SDNN in 27 subjects (−33.9 ms; P & lt; 0.001, paired analysis); decreased RMSSD (−0.3 log-ms; P = 0.025); and increased the mean HR (8.1 beats/min; P = 0.003), daytime HR (5.7; P = 0.083), and nighttime HR (6.3; P = 0.026). In a multivariable regression analysis, the decrease in SDNN remained significant after adjustment for metabolic and HR changes. Liraglutide reduced HF power (−0.7 log-ms2; P = 0.026) without any change in LF/HF ratio. CONCLUSIONS In overweight patients with CAD and newly diagnosed T2D, liraglutide increased HR and reduced HRV despite significant weight loss and improvement in metabolic parameters. The increase in nightly HR in conjunction with a decrease in parameters of parasympathetic activity suggests that liraglutide may affect sympathovagal balance.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc16-1580
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2017
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  • 6
    Online Resource
    Online Resource
    Basal and Insulin Mediated VLDL-Triglyceride Kinetics in Type 2 Diabetic Men
    American Diabetes Association ; 2011
    In:  Diabetes Vol. 60, No. 1 ( 2011-01-01), p. 88-96
    Details
    In: Diabetes, American Diabetes Association, Vol. 60, No. 1 ( 2011-01-01), p. 88-96
    Abstract: Increased very-low-density lipoprotein triglycerides (VLDL-TG) concentration is a central feature of diabetic dyslipidemia. The objective was to compare basal and insulin mediated VLDL-TG kinetics, oxidation, and adipose tissue storage in type 2 diabetic and healthy (nondiabetic) men. RESEARCH DESIGN AND METHODS Eleven type 2 diabetic and 11 healthy men, matched for BMI and age, were included. Ex vivo-labeled VLDL-TG tracers, blood and breath samples, fat biopsies, indirect calorimetry, and body composition measures were applied to determine VLDL-TG kinetics, VLDL-TG fatty acids (FA) oxidation, and storage in regional adipose tissue before and during a hyperinsulinemic euglycaemic clamp. RESULTS VLDL-TG secretion was significantly greater in diabetic compared with healthy men (basal: 86.9 [31.0] vs. 61.9 [30.0] μmol/min, P = 0.03; clamp: 60.0 [26.2] vs. 34.2 [17.9] μmol · min−1, P = 0.01). The insulin mediated suppression of VLDL-TG secretion was significant in both groups. VLDL-TG clearance was lower in diabetic men (basal: 84.6 [32.7] vs. 115.4 [44.3] ml · min−1, P = 0.08; clamp: 76.3 [30.6] vs. 119.0 [50.2] ml · min−1, P = 0.03). During hyperinsulinemia fractional VLDL-TG FA oxidation was comparable, but in percentage of energy expenditure (EE), significantly higher in diabetic men. Basal VLDL-TG storage was similar, but significantly greater in abdominal compared with leg fat. CONCLUSIONS Increased VLDL-TG in type 2 diabetic men is caused by greater VLDL-TG secretion and less so by lower VLDL-TG clearance. The ability of hyperinsulinemia to suppress VLDL-TG secretion appears preserved. During hyperinsulinemia VLDL-TG FA oxidation is significantly increased in proportion of EE in type 2 diabetic men. Greater basal abdominal VLDL-TG storage may help explain the accumulation of upper-body fat in insulin-resistant individuals.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db10-0564
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2011
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  • 7
    Online Resource
    Online Resource
    Diabetes Incidence and Long-Term Exposure to Air Pollution
    American Diabetes Association ; 2012
    In:  Diabetes Care Vol. 35, No. 1 ( 2012-01-01), p. 92-98
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 35, No. 1 ( 2012-01-01), p. 92-98
    Abstract: Animal and cross-sectional epidemiological studies suggest a link between air pollution and diabetes, whereas the limited prospective data show mixed results. We studied the association between long-term exposure to traffic-related air pollution and incidence of diabetes. RESEARCH DESIGN AND METHODS We followed 57,053 participants of the Danish Diet, Cancer, and Health cohort in the Danish National Diabetes Register between baseline (1993–1997) and 27 June 2006. We estimated the mean levels of nitrogen dioxide (NO2) at the residential addresses of the cohort participants since 1971 and modeled the association between NO2 and diabetes incidence with a Cox regression model, separately for two definitions of diabetes: all cases and a more strict definition where unconfirmed cases were excluded. RESULTS Over a mean follow-up of 9.7 years of 51,818 eligible subjects, there were 4,040 (7.8%) incident diabetes cases in total and 2,877 (5.5%) with confirmed diagnoses. Air pollution was not associated with all diabetes cases (hazard ratio 1.00 [95% CI 0.97–1.04] per interquartile range of 4.9 μg/m3 mean NO2 levels since 1971), but a borderline statistically significant association was detected with confirmed cases of diabetes (1.04 [1.00–1.08] ). Among confirmed diabetes cases, effects were significantly enhanced in nonsmokers (1.12 [1.05–1.20]) and physically active people (1.10 [1.03–1.16] ). CONCLUSIONS Long-term exposure to traffic-related air pollution may contribute to the development of diabetes, especially in individuals with a healthy lifestyle, nonsmokers, and physically active individuals.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc11-1155
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2012
    detail.hit.zdb_id: 1490520-6
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