Plasma Copeptin and the Risk of Diabetes Mellitus

In the paper

“pharmacological blockade of the V2R, a potent stimulus of increased AVP secretion,35 was associated with a 5% incidence in hyperglycemic events during 30 days of tolvaptan treatment in patients with hyponatremia compared to 1% in controls, although numbers were small (12/223 vs 2/220).8”

What the sources say

• Supported

  Table 3 in the adverse-events and safety section reports hyperglycemia in 12 of 223 tolvaptan recipients (5%) and 2 of 220 placebo recipients (1%). The Methods describe a 30-day trial in patients with hyponatremia. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites [8] source
• ?Not checked — no full text of the sourcecites [35] source

In the paper

“On the other hand, given the strict HbA1c criteria for new-onset diabetes in the MHR and the fact that the NDR and Diabetes 2000 registers require a physician diagnosis according to established diagnostic criteria,28, 29 those classified as new-onset diabetes cases in our study are unlikely to be misclassified.”

What the sources say

• Partly supported

  The Research Design and Methods section says NDR data are reported by trained physicians and nurses during clinical visits and gives this study’s definition of type 2 diabetes. It does not say that NDR registration requires a physician diagnosis according to established diagnostic criteria. The MHR criteria and the citing authors’ inference about misclassification are not claims this citation specifically supports. (LLM, conf=0.82)

  cites [28] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [29] source

In the paper

“Continuous copeptin concentration at baseline was significantly higher in subjects who subsequently developed new-onset diabetes compared with those who did not, regardless of whether subjects with IFG at baseline were included (Table 3).”

In the paper

“The odds of insulin resistance increased with increasing copeptin in both crude analysis and after adjustment for model 1 covariates and FBG (Table 2).”

In the paper

“The association with incident diabetes remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios 1.0, 1.80, 1.92, and 3.48; P=0.001).”

In the paper

“and from 0.832 to 0.841 (P=0.007) when copeptin was added to the clinical model of diabetes prediction.”

In the paper

“In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes (P=0.04) and insulin resistance (P<0.001).”

• Also stated in: § RESULTS · plain

  “The odds of insulin resistance increased with increasing copeptin in both crude analysis and after adjustment for model 1 covariates and FBG (Table 2).”

In the paper

“In subjects free of diabetes at baseline, the area under the ROC curve increased from 0.694 to 0.710 (P=0.08) when copeptin was added to the personal model”

In the paper

“Nonetheless, after accounting for FBG and all other available diabetes risk factors, individuals in the top quartile of copeptin had a two- to three-fold excess risk of developing diabetes compared with those in the lowest quartile of copeptin.”

In the paper

“With addition of copeptin, the C-statistic from Cox regression models increased in subjects without diabetes at baseline from 0.702 to 0.718 in the personal model and from 0.835 to 0.844 in the clinical model.”

In the paper

“At the baseline examination, concentrations of copeptin were higher among individuals with diabetes compared with subjects without diabetes (Table 1).”

In the paper

“The odds of developing diabetes increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios 1.0, 1.37, 1.79, and 2.09; P for trend =0.004).”

In the paper

“The improvement in the area under the ROC curve was smaller when the entire sample, including those with IFG, was considered.”

In the paper

“During 12.6 years of follow up 174 subjects (4%) developed new-onset diabetes.”

• Also stated in: § RESULTS · plain

  “Among participants free of diabetes at baseline (n=4377), 174 subjects developed new-onset diabetes (Table 3) according to the three different registers.”

In the paper

“In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes (P=0.04) and insulin resistance (P<0.001).”

In the paper

“in healthy subjects AVP infusion leads to increased blood glucose levels.19”

What the sources say

• ?Not checked — no full text of the sourcecites [19] source

In the paper

“Finally, Cox regression models were performed in order to exclude potential bias related to inter-individual differences in follow-up time in the logistic regressions models and the results were unchanged (Supplemental Table 1).”

In the paper

“This finding may result from FBG being a more powerful predictor of diabetes at FBG levels near the diagnostic limit of 6.1mmol/L.”

In the paper

“In patients with poorly controlled diabetes mellitus, plasma AVP is markedly elevated18”

What the sources say

• ?Not checked — no full text of the sourcecites [18] source

In the paper

“Elevated copeptin predicts increased risk for diabetes, independent of established clinical risk factors, including fasting glucose and insulin.”

• Also stated in: § DISCUSSION · plain

  “The key finding of our study is that copeptin predicts diabetes development independently of renal function and a broad range of diabetes risk factors at baseline, including FBG and fasting insulin.”

• Also stated in: § DISCUSSION · plain

  “In conclusion, copeptin predicts diabetes independently of a broad range of established diabetes risk factors, including fasting levels of glucose and insulin.”

In the paper

“Previous studies in humans and animals have suggested a role for the AVP system in glucose homeostasis, insulin resistance and diabetes mellitus.”

• Also stated in: § Background · hedged

  “Animal studies suggest that the arginine vasopressin (AVP) system may play a role in glucose metabolism, but data from humans are limited.”

In the paper

“Apart from any implications for diabetes prediction, our data support a role for the AVP system in the pathophysiology of diabetes.”

In the paper

“Markers that are not part of the diagnostic criteria for diabetes, such as copeptin, may better signal diabetes susceptibility earlier in the pre-diabetes state.”

In the paper

“The diabetes incidence in our study may appear low but was comparable with that in a previous Swedish study.36”

What the sources say

• ?Not checked — no full text of the sourcecites [36] source

In the paper

“The validity of the register based new-onset diabetes diagnosis is further supported by most of the well-known risk factors for diabetes being markedly elevated at the MDC-CC baseline in these subjects as compared to those who did not develop diabetes according to the three registers (Table 3).”

In the paper

“The fact that we were able to reproduce the association between copeptin and the register-based diabetes endpoint, using a FBG-based endpoint in a subset of MDC-CC, strongly supports the validity of our findings.”

In the paper

“These factors would be expected to bias our results towards the null.”

In the paper

“In addition, our results highlight the possibility that existing therapies that selectively antagonize AVP receptors could have metabolic side effects.”

In the paper

“Thus, our findings suggest that copeptin could provide incremental information for prediction of diabetes.”