Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study

Huemer, Marie-Theres; Huth, Cornelia; Schederecker, Florian; Klug, Stefanie J.; Meisinger, Christa; Köenig, Wolfgang; Rathmann, Wolfgang; Peters, Annette; Thorand, Barbara

doi:10.1136/bmjdrc-2020-001321

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…(3) Higher serum ALP levels had been reported to be associated with increased inflammation status in CKD patients or general population [ 36 , 37 ]. Notably, both endothelial dysfunction [ 38 , 39 ] and chronic inflammation [ 40 , 41 ] has been considered as the early events in the development of the diabetes. Taken together, the aforementioned biological functions of ALP may be in part underlying our observed positive association between ALP and incident diabetes.…”

Section: Discussionmentioning

confidence: 99%

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Zhang

Zhou

et al. 2020

Cardiovasc Diabetol

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Background The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults. Methods A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG < 6.1 mmol/L at baseline and ≥ 6.1 but < 7.0 mmol/L at the exit visit. Results Over a median of 4.5 years follow-up, 1549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95% CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95% CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) < 10 μmol/L (adjusted OR, 1.24; 95% CI: 1.10, 1.40 vs. ≥ 10 μmol/L: adjusted OR, 1.03; 95% CI: 0.96, 1.10; P-interaction = 0.007) or FG ≥ 5.9 mmol/L (adjusted OR, 1.16; 95% CI: 1.07, 1.27 vs. < 5.9 mmol/L: adjusted OR, 1.00; 95% CI: 0.93, 1.08; P-interaction = 0.009) Conclusions In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels. Clinical Trial Registration-URL Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.

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Section: Discussionmentioning

confidence: 99%

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Zhang

Zhou

et al. 2020

Cardiovasc Diabetol

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“…(3) Higher serum ALP levels had been reported to be associated with increased in ammation status in CKD patients or general population [27,28]. Notably, both endothelial dysfunction [29,30] and chronic in ammation [31,32] has been considered as the early events in the development of the diabetes. Taken together, the aforementioned biological functions of ALP may be in part underlying our observed positive association between ALP and incident diabetes.…”

Section: Discussionmentioning

confidence: 99%

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Zhang

Zhou

et al. 2020

Preprint

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Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults. Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG <6.1mmol/L at baseline and ≥6.1 but <7.0mmol/L at the exit visit.Results: Over a median of 4.5 years follow-up, 1,549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95%CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95%CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) <10μmol/L (adjusted OR, 1.24; 95%CI: 1.10, 1.40 vs. ≥10μmol/L: adjusted OR, 1.03; 95%CI: 0.96, 1.10; P-interaction=0.007) or FG ≥5.9mmol/L (adjusted OR, 1.16; 95%CI: 1.07, 1.27 vs. <5.9mmol/L: adjusted OR, 1.00; 95%CI: 0.93, 1.08; P-interaction =0.009)Conclusions: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.Clinical Trial Registration-URL: Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.

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“…Insulin levels were measured in serum using an eletrochemiluminescence immunoassay on a Cobas e602 instrument (Roche) or a solid‐phase enzyme‐labeled chemiluminescent immunometric assay on Immulite 2000 systems analyzer (Siemens). Homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated as (fasting insulin [mU/L] × fasting glucose [mmol/L]/22.5) 18,20,21 …”

Section: Methodsmentioning

confidence: 99%

“…Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as (fasting insulin [mU/L] × fasting glucose [mmol/L]/22.5). 18,20,21 HOMA-IR was categorized into insulin sensitive (HOMA-IR <2.5) and insulin resistant (HOMA-IR ≥2.5) whereas HbA1c was categorized into normal (HbA1c <5.7%), prediabetes (HbA1c ≥5.7% and <6.5%), and diabetes (HbA1c ≥6.5%). 22,23 Doctor-diagnosed asthma and rhinitis were defined as affirmative answers to the question "Have you ever been diagnosed with asthma by a physician?"…”

Section: Study Populationmentioning

confidence: 99%

Differential effects of lung inflammation on insulin resistance in humans and mice

Karlina

Flexeder

Musiol

et al. 2022

Allergy

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Background:The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis.Methods: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were Funding informationThe KORA study was initiated and financed by the Helmholtz Zentrum München-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Mouse studies were supported by the HMGU Allergy Projects from the Helmholtz Center Munich.intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues. Results:We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1.Conclusions: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis.

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Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study

Cited by 10 publications

References 38 publications

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Differential effects of lung inflammation on insulin resistance in humans and mice

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