Type 2 diabetes: one disease, many pathways

Ha, Joon; Sherman, Arthur

doi:10.1152/ajpendo.00512.2019

Cited by 49 publications

(60 citation statements)

References 80 publications

(110 reference statements)

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“…ALP serum alkaline phosphatase, CI confidence interval, eGFR estimated glomerular filtration rate, RR risk ratio, SD standard deviations, SBP systolic blood pressure *Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period tHcy (< 10 μmol/L) or higher FG (≥ 5.9 mmol/L) levels at baseline. The higher FG levels may partially represent the abnormal glucose metabolic state, due to the impairment of pancreatic alpha and beta cell function and the induced impaired insulin secretion [42,43]. This population usually had a significantly increased risk of diabetes [44].…”

Section: Table 4 Estimating the Association Between Baseline Serum Almentioning

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: Table 4 Estimating the Association Between Baseline Serum Almentioning

confidence: 99%

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

Zhang

Zhou

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…A stronger association was found in those with lower tHcy (< 10 µmol/L) or higher FG (≥ 5.9 mmol/L) levels at baseline. The higher FG levels may partially represent the abnormal glucose metabolic state, due to the impairment of pancreatic alpha and beta cell function and the induced impaired insulin secretion [33,34]. This population usually had a signi cantly increased risk of diabetes [35].…”

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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“…Ha's model has been recently expanded (Ha and Sherman, 2020) to enrich the glucose homeostasis model, including a dynamic β-cell response [based on Chen et al (2008)]. The model describes more precisely glucose and insulin concentration obtained from experimental studies, including the OGTT and the IVGTT, allowing prediction of fasting and 2-h glucose after an OGTT both at a given time point and longitudinally, similarly to the model by De Gaetano and Hardy (2019).…”

Section: β-Cell Function Deteriorationmentioning

confidence: 99%

Mathematical Modeling for the Physiological and Clinical Investigation of Glucose Homeostasis and Diabetes

et al. 2020

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Mathematical modeling in the field of glucose metabolism has a longstanding tradition. The use of models is motivated by several reasons. Models have been used for calculating parameters of physiological interest from experimental data indirectly, to provide an unambiguous quantitative representation of pathophysiological mechanisms, to determine indices of clinical usefulness from simple experimental tests. With the growing societal impact of type 2 diabetes, which involves the disturbance of the glucose homeostasis system, development and use of models in this area have increased. Following the approaches of physiological and clinical investigation, the focus of the models has spanned from representations of whole body processes to those of cells, i.e., from in vivo to in vitro research. Model-based approaches for linking in vivo to in vitro research have been proposed, as well as multiscale models merging the two areas. The success and impact of models has been variable. Two kinds of models have received remarkable interest: those widely used in clinical applications, e.g., for the assessment of insulin sensitivity and β-cell function and some models representing specific aspects of the glucose homeostasis system, which have become iconic for their efficacy in describing clearly and compactly key physiological processes, such as insulin secretion from the pancreatic β cells. Models are inevitably simplified and approximate representations of a physiological system. Key to their success is an appropriate balance between adherence to reality, comprehensibility, interpretative value and practical usefulness. This has been achieved with a variety of approaches. Although many models concerning the glucose homeostasis system have been proposed, research in this area still needs to address numerous issues and tackle new opportunities. The mathematical representation of the glucose homeostasis processes is only partial, also because some mechanisms are still only partially understood. For in vitro research, mathematical models still need to develop their potential. This review illustrates the problems, approaches and contribution of mathematical modeling to the physiological and clinical investigation of glucose homeostasis and diabetes, focusing on the most relevant and stimulating models.

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Type 2 diabetes: one disease, many pathways

Cited by 49 publications

References 80 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

Mathematical Modeling for the Physiological and Clinical Investigation of Glucose Homeostasis and Diabetes

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