the prevalence of type 2 diabetes ( t2 dm ) is currently estimated to be 8.3% worldwide and has increased rapidly over past decades .
this coincides with changes in lifestyle behaviours including an increased consumption of processed foods and a decreased intake of fruit and vegetables .
fruit and vegetables contain a number of potentially beneficial components , including potassium ( k ) , a major intracellular cation of the body .
previous observational studies have investigated the relationship between serum k , glucose regulation , and risk of t2 dm [ 3 , 4 ] . the atherosclerosis risk in the communities ( aric ) study demonstrated an inverse association between serum k and fasting insulin levels , and risk of t2 dm ; this relationship was confirmed in the topics 1 study .
however a recent study which investigated k in individuals with impaired glucose regulation only found a significant relationship in those with established hypertension . to help clarify the evidence we aimed to determine whether an association existed between serum k and glucose regulation within a uk multiethnic population
; this is the first uk study to conduct analysis in a high risk population and thus extends the literature available .
participants were recruited as part of the addition leicester study , a population based screening study that formed part of addition - europe , described in detail elsewhere .
all individuals were given a 75  g oral glucose load after an overnight fast and diagnosis of diabetes was made according to 1999 who criteria .
plasma glucose was determined using the hexokinase method ( abbott laboratories , maidenhead , uk ; coefficient of variation ( cv ) 1.61% ) .
hba1c was quantified using high performance liquid chromatography on an automated dcct aligned biorad aligned system ( biorad laboratories , hemel hempstead , uk ; cv < 0.1% ) .
serum total , hdl , ldl - cholesterol , and triglycerides were measured by enzymatic methods ( dade behring dimension analyser , newark , usa ) .
serum potassium was measured using a siemens advia 2400 clinical chemistry system ( siemens health care , germany ; cv < 1% ) .
analyses were conducted in the pathology laboratories of the university hospitals of leicester , nhs trust , uk .
the study was conducted according to the guidelines laid down in the declaration of helsinki and all procedures involving human subjects were approved by leicestershire , rutland , and northamptonshire research ethics committee . written informed consent was obtained from all subjects .
tests for associations between baseline characteristics and k quartiles ( < 4.0  mmol / l , 4.04.2  mmol / l , 4.34.4  mmol / l , and 4.5 
mmol / l ) were conducted using linear regression models : ( 1 ) unadjusted ; ( 2 ) adjusted for baseline measures of average systolic and diastolic blood pressure and for cockcroft - gault estimated glomerular filtration rate ; ( 3 ) adjusted for the previous confounders plus ethnicity , sex , age , and bmi . in sensitivity analyses we restricted the estimations in the subset of participants with normal glucose regulation at baseline ( n = 5,249 ) and in those who were not taking any blood pressure medication ( diuretics / thiazides , ace - inhibitors , beta - blockers , or angiotensin - ii receptor antagonists ) ( n = 5,187 ) . two sided p - value of < 0.05 was considered statistically significant .
from 6,749 individuals screened for diabetes we excluded those with missing k data ( n = 154 ) , those with k greater than 5.5  mmol / l ( n = 62 ) , and those with renal dysfunction ( creatinine level > 1.7  mg / dl ( 150  mol / l ) ( n = 13 ) , thus leaving 6,520 participants for the analyses . of these 4,523 ( 69.4% ) were white european and 1,629 ( 25.0% ) were south asian .
baseline characteristics are presented in table 1 for the whole population and separately by k quartile . at screening 5,249 ( 81% ) had normal glucose tolerance , 1,054 ( 16% ) had impaired glucose regulation , and 205 ( 3% ) were newly diagnosed with t2 dm . participants in the lowest k quartile had significantly greater 2-hour glucose levels than those in the highest k quartile ( 0.53  mmol / l , 95% confidence interval ( ci ) : 0.36 to 0.70 , p  0.001 ; tables 1 and 2 ) .
this estimation did not change with adjustment for potential confounders ; model ( 2 ) : 0.49  mmol / l ; 95% ci : 0.29 to 0.63 ; p  0.001 and model ( 3 ) : 0.49  mmol / l ; 95% ci : 0.33 to 0.66 ; p  0.001 . conversely those in the lowest k quartile had a 0.14% lower hba1c ( 95% ci : 0.19 to 0.10 : 0 .
p  0.001 ) compared to those in the highest k quartile ; again adjustment for confounders did not alter the association ( table 3 ) .
there was no association between k quartiles and fasting blood glucose in either the unadjusted or the adjusted models ( table 4 ) .
sensitivity analyses restricted to participants with normal glucose regulation and excluding participants taking antihypertensive medication , including thiazides , did not change the results ( data not shown ) .
this cross - sectional analysis of individuals who were screened for t2 dm demonstrated that lower k was associated with greater 2  hr glucose .
no associations were observed between fasting plasma glucose and k. in contrast those with greater k had higher hba1c ; however , although statistically significantly different , a change of 0.14% hba1c is unlikely to be considered clinically relevant .
the discrepancy between findings in 2  hr glucose and hba1c could likely reflect the greater sensitivity of the 2  hr glucose to insulin secretion ; indeed this process is controlled by atp - sensitive potassium channels .
additional subanalysis solely of those with normal glucose tolerance at baseline further showed that in otherwise healthy individuals low serum k was associated with greater 2  hr glucose , suggesting that low serum k may be implicated in the development of impaired glucose regulation .
prospective studies have previously observed that low baseline k levels are predictive of development of t2 dm [ 4 , 5 ] .
this study provides a unique dataset of subjects from a multiethnic population ; we have conducted analysis to account for potential confounding variables and carried out sensitivity analysis to exclude those taking antihypertensive medication which may influence k concentrations .
nonetheless several limitations should be mentioned ; the measurement of k was from a single blood sample at the baseline visit ; however stringent laboratory conditions were in place to ensure the accuracy of samples .
information on dietary k consumption or the intake of supplements which may include k was not available .
it is also important to note all levels of k in our study were within normal physiological levels .
we excluded those with creatinine levels greater or equal to 1.7  mg / dl , thus attempting to exclude renal impairment as a potentially confounding factor .
indeed the population appears relatively healthy ( mean blood pressure of the cohort is within the normal range ) , and this should be considered when comparing the data to other populations . finally this study is cross - sectional by design ; therefore we can not determine the direction of association ; however available data supports the possibility that k may influence glucose regulation and further research is warranted .
 
 introduction . 
 previous observational studies have shown conflicting results between plasma k+ concentrations and risk of type 2 diabetes . to help clarify the evidence we aimed to determine whether an association existed between serum k+ and glucose regulation within a uk multiethnic population . 
 methods . 
 participants were recruited as part of the addition leicester study , a population based screening study . 
 individuals from primary care between the age of 40 and 75 years if white european or 25 and 75 years if south asian or afro caribbean were recruited . 
 tests for associations between baseline characteristics and k+ quartiles were conducted using linear regression models . 
 results . 
 data showed individuals in the lowest k+ quartile had significantly greater 2-hour glucose levels ( 0.53  mmol / l , 95% ci : 0.36 to 0.70 , p  0.001 ) than those in the highest k+ quartile . 
 this estimation did not change with adjustment for potential confounders . 
 conversely , participants in the lowest k+ quartile had a 0.14% lower hba1c ( 95% ci 0.19 to 0.10 : p  0.001 ) compared to those in the highest k+ quartile . conclusion . 
 this cross - sectional analysis demonstrated that lower k+ was associated with greater 2  hr glucose . 
 the data supports the possibility that k+ may influence glucose regulation and further research is warranted . 
1. Introduction 
2. Materials and Methods
3. Statistical Analysis
4. Results
5. Discussion