Int Urol Nephrol DOI 10.1007/s11255-015-1001-5
NEPHROLOGY - ORIGINAL PAPER
A relationship between serum potassium concentration and insulin resistance in patients with type 2 diabetes mellitus Hyun Woo Kim1 · Dae Ho Lee2 · Sang Ah Lee1 · Gwanpyo Koh1
Received: 25 January 2015 / Accepted: 26 April 2015 © Springer Science+Business Media Dordrecht 2015
Abstract Purpose In patients with type 2 diabetes mellitus (DM), insulin-stimulated glucose uptake is impaired. However, the relationship between serum potassium concentration and insulin resistance is poorly defined. This study aimed to investigate the association between serum potassium concentration and insulin resistance in these patients. Methods Between April 2009 and October 2012, 180 patients with type 2 DM were analyzed. Insulin resistance was estimated using the homeostasis model and assessment (HOMA) index; resistance was defined as an index value of >2. The association between serum potassium concentration and insulin resistance was analyzed using linear regression methods. The incidence of hyperkalemia was also evaluated during follow-up. Results Mean serum potassium concentration was 4.12 ± 0.47 mEq/l. The median HOMA index score was 2.1 (interquartile range 1.1–3.4). When the patients were compared based on insulin resistance, serum potassium concentration was higher in the patients with insulin resistance compared with the patients without (4.25 ± 0.48 vs. 4.09 ± 0.44 mEq/l, p = 0.015). The variables found to be the determinants of serum potassium concentration included female, renal function, serum sodium level, log * Gwanpyo Koh [email protected] Hyun Woo Kim [email protected] 1
Department of Internal Medicine, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju City, Jeju 690‑756, Republic of Korea
2
Department of Internal Medicine, College of Medicine, Wonkwang University, 460 Iksan‑daero, Iksan‑si, Jeollabuk‑do 570‑740, Republic of Korea
aldosterone-to-plasma renin activity ratio, glycosylated hemoglobin, and log HOMA index. Over a mean follow-up period of 2.6 ± 1.1 years, 37 of 180 patients (21 %) experienced episodic hyperkalemia. Patients with insulin resistance experienced episodic hyperkalemia more frequently than those without. Conclusions Serum potassium concentration is likely to be increased in the patients with poorly controlled type 2 DM with insulin resistance than in those without insulin resistance. Keywords Diabetes mellitus type 2 · Insulin resistance · Potassium
Introduction In healthy adults, the serum potassium level is strictly controlled within a narrow range of 3.5–5.5 mEq/l [1]. This is achieved by two maintaining mechanisms that regulate potassium level irrespective of the dietary potassium intake. First, ingested potassium stimulates insulin release and elevated insulin levels induce rapid transport of potassium from the extracellular space into cells. Second, increased serum potassium stimulates the renin-angiotensin-aldosterone system (RAAS) and causes the renal cortical collecting ducts to excrete potassium. Therefore, compromised renal function and hypoaldosteronism predispose to hyperkalemia [2]. In addition, it is known that the homeostatic mechanisms for handling potassium are impaired in patients with diabetes mellitus (DM). This is because of DM itself, in which insulin deficiency limits potassium movement from plasma to the cells, thus increasing the risk of serum potassium elevation [3]; combined renal diseases, which are expressed through distal tubular potassium
13
excretion defects because of hyporeninemic hypoaldosteronism or tubular insensitivity to aldosterone [4]; and medications such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin two receptor blockers (ARBs) [5]. Insulin is a key defender against exogenous potassium load through intracellular buffering to minimize hyperkalemia before renal excretion [6]. Thus, an insulindeficient state in type 1 DM predisposes to hyperkalemia because it impairs the ability of potassium to enter cells [4]. Although in patients with type 2 DM, insulin-stimulated glucose uptake is impaired [7], the relationship between serum potassium concentration and insulin resistance is poorly defined in these patients. Thus, this study aimed to investigate the association between serum potassium concentration and insulin resistance in patients with type 2 DM. We also observed the development of episodic hyperkalemia during the follow-up period.
Patients and methods Patients Patients who were admitted in our hospital endocrinology metabolism clinic with type 2 DM from April 2009 to October 2012 were studied. Patients were excluded if they were treated with insulin or had type 1 DM. In addition, we excluded patients without adequate follow-up data (>1 year follow-up data including two or more serum potassium measurements). In the remaining 180 patients with type 2 DM, a cross-sectional analysis was performed to examine the relationship between serum potassium and insulin resistance. The incidence of hyperkalemia was also evaluated during follow-up period. This study was approved by an institutional review board (no. JEJUNUH 2010-33). Data collection Data collected on patients included age, sex, blood pressure, height, weight, personal medical history, and medications taken. Serum electrolytes, blood urea nitrogen (BUN), serum creatinine, glycosylated hemoglobin (HbA1c), fasting glucose and insulin concentrations, 24-h urine protein, urine electrolytes, serum and urine osmolalities, plasma renin activity, and serum aldosterone level were measured for this study. Blood samples for measuring serum concentrations of glucose and insulin were collected after an overnight fast and those for plasma renin activity and plasma aldosterone were taken after the patients had remained in a sitting position for 10 min. In addition, the prescription status at the time of admission and during the study period was investigated. Insulin resistance was estimated by using the homeostasis model and assessment (HOMA) index with
13
Int Urol Nephrol
the formula described by Matthews et al. [8] (HOMA index score = insulin mU/l × glucose mmol/l/22.5). As few studies have attempted to define insulin resistance in the adult Korean population, patients were divided according to the HOMA index score using an arbitrary cutoff point of 2.0. The transtubular potassium gradient (TTKG) was calculated according to the formula: TTKG = urine potassium/ (urine osmolality/plasma osmolality)/plasma potassium [9]. Renal function was evaluated by the estimated glomerular filtration rate (eGFR), using the modification of diet in renal disease formula [10]. Our laboratory normal ranges of sitting plasma renin activity and serum aldosterone level are 0.24–4.70 ng/mL/h and 40–310 pg/ml, respectively. Hyperkalemia is defined as an elevation in serum potassium to a value >5.5 mEq/l [11]. Statistics The patients were divided into 2 groups on the basis of HOMA index values greater or less than 2.0. Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR). Categorical variables were presented as frequencies and percentages. Student’s t test or the Mann–Whitney U test was used to compare differences in continuous variables. The Chisquare test or Fisher’s exact test was used to compare categorical variables. To assess cross-sectional relationships between serum potassium and clinical parameters such as age, sex, eGFR, fasting glucose and insulin concentrations, serum bicarbonate concentration, serum aldosterone level, albuminuria, the use of ACEIs or ARBs, the use of aldosterone receptor blockers such as spironolactone, the use of diuretics (loop and/or hydrochlorothiazide), and insulin resistance assessed by HOMA index score, simple linear regression analysis was performed first, after which multiple regression analysis was carried out using a stepwise selection process. The incidence of hyperkalemia during follow-up period was also evaluated. The data including prescription status at the time of the development of hyperkalemia were used for the analysis and comparison between patients with insulin resistance and those without. Variables that can affect potassium concentration such as age, sex, the presence of hypertension and diabetic nephropathy, renal function, drugs (RAAS inhibitors, β-blockers, diuretics and insulin), and insulin resistance were analyzed with logistic regression analysis. Statistical significance was defined as a p value
NEPHROLOGY - ORIGINAL PAPER
A relationship between serum potassium concentration and insulin resistance in patients with type 2 diabetes mellitus Hyun Woo Kim1 · Dae Ho Lee2 · Sang Ah Lee1 · Gwanpyo Koh1
Received: 25 January 2015 / Accepted: 26 April 2015 © Springer Science+Business Media Dordrecht 2015
Abstract Purpose In patients with type 2 diabetes mellitus (DM), insulin-stimulated glucose uptake is impaired. However, the relationship between serum potassium concentration and insulin resistance is poorly defined. This study aimed to investigate the association between serum potassium concentration and insulin resistance in these patients. Methods Between April 2009 and October 2012, 180 patients with type 2 DM were analyzed. Insulin resistance was estimated using the homeostasis model and assessment (HOMA) index; resistance was defined as an index value of >2. The association between serum potassium concentration and insulin resistance was analyzed using linear regression methods. The incidence of hyperkalemia was also evaluated during follow-up. Results Mean serum potassium concentration was 4.12 ± 0.47 mEq/l. The median HOMA index score was 2.1 (interquartile range 1.1–3.4). When the patients were compared based on insulin resistance, serum potassium concentration was higher in the patients with insulin resistance compared with the patients without (4.25 ± 0.48 vs. 4.09 ± 0.44 mEq/l, p = 0.015). The variables found to be the determinants of serum potassium concentration included female, renal function, serum sodium level, log * Gwanpyo Koh [email protected] Hyun Woo Kim [email protected] 1
Department of Internal Medicine, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju City, Jeju 690‑756, Republic of Korea
2
Department of Internal Medicine, College of Medicine, Wonkwang University, 460 Iksan‑daero, Iksan‑si, Jeollabuk‑do 570‑740, Republic of Korea
aldosterone-to-plasma renin activity ratio, glycosylated hemoglobin, and log HOMA index. Over a mean follow-up period of 2.6 ± 1.1 years, 37 of 180 patients (21 %) experienced episodic hyperkalemia. Patients with insulin resistance experienced episodic hyperkalemia more frequently than those without. Conclusions Serum potassium concentration is likely to be increased in the patients with poorly controlled type 2 DM with insulin resistance than in those without insulin resistance. Keywords Diabetes mellitus type 2 · Insulin resistance · Potassium
Introduction In healthy adults, the serum potassium level is strictly controlled within a narrow range of 3.5–5.5 mEq/l [1]. This is achieved by two maintaining mechanisms that regulate potassium level irrespective of the dietary potassium intake. First, ingested potassium stimulates insulin release and elevated insulin levels induce rapid transport of potassium from the extracellular space into cells. Second, increased serum potassium stimulates the renin-angiotensin-aldosterone system (RAAS) and causes the renal cortical collecting ducts to excrete potassium. Therefore, compromised renal function and hypoaldosteronism predispose to hyperkalemia [2]. In addition, it is known that the homeostatic mechanisms for handling potassium are impaired in patients with diabetes mellitus (DM). This is because of DM itself, in which insulin deficiency limits potassium movement from plasma to the cells, thus increasing the risk of serum potassium elevation [3]; combined renal diseases, which are expressed through distal tubular potassium
13
excretion defects because of hyporeninemic hypoaldosteronism or tubular insensitivity to aldosterone [4]; and medications such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin two receptor blockers (ARBs) [5]. Insulin is a key defender against exogenous potassium load through intracellular buffering to minimize hyperkalemia before renal excretion [6]. Thus, an insulindeficient state in type 1 DM predisposes to hyperkalemia because it impairs the ability of potassium to enter cells [4]. Although in patients with type 2 DM, insulin-stimulated glucose uptake is impaired [7], the relationship between serum potassium concentration and insulin resistance is poorly defined in these patients. Thus, this study aimed to investigate the association between serum potassium concentration and insulin resistance in patients with type 2 DM. We also observed the development of episodic hyperkalemia during the follow-up period.
Patients and methods Patients Patients who were admitted in our hospital endocrinology metabolism clinic with type 2 DM from April 2009 to October 2012 were studied. Patients were excluded if they were treated with insulin or had type 1 DM. In addition, we excluded patients without adequate follow-up data (>1 year follow-up data including two or more serum potassium measurements). In the remaining 180 patients with type 2 DM, a cross-sectional analysis was performed to examine the relationship between serum potassium and insulin resistance. The incidence of hyperkalemia was also evaluated during follow-up period. This study was approved by an institutional review board (no. JEJUNUH 2010-33). Data collection Data collected on patients included age, sex, blood pressure, height, weight, personal medical history, and medications taken. Serum electrolytes, blood urea nitrogen (BUN), serum creatinine, glycosylated hemoglobin (HbA1c), fasting glucose and insulin concentrations, 24-h urine protein, urine electrolytes, serum and urine osmolalities, plasma renin activity, and serum aldosterone level were measured for this study. Blood samples for measuring serum concentrations of glucose and insulin were collected after an overnight fast and those for plasma renin activity and plasma aldosterone were taken after the patients had remained in a sitting position for 10 min. In addition, the prescription status at the time of admission and during the study period was investigated. Insulin resistance was estimated by using the homeostasis model and assessment (HOMA) index with
13
Int Urol Nephrol
the formula described by Matthews et al. [8] (HOMA index score = insulin mU/l × glucose mmol/l/22.5). As few studies have attempted to define insulin resistance in the adult Korean population, patients were divided according to the HOMA index score using an arbitrary cutoff point of 2.0. The transtubular potassium gradient (TTKG) was calculated according to the formula: TTKG = urine potassium/ (urine osmolality/plasma osmolality)/plasma potassium [9]. Renal function was evaluated by the estimated glomerular filtration rate (eGFR), using the modification of diet in renal disease formula [10]. Our laboratory normal ranges of sitting plasma renin activity and serum aldosterone level are 0.24–4.70 ng/mL/h and 40–310 pg/ml, respectively. Hyperkalemia is defined as an elevation in serum potassium to a value >5.5 mEq/l [11]. Statistics The patients were divided into 2 groups on the basis of HOMA index values greater or less than 2.0. Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR). Categorical variables were presented as frequencies and percentages. Student’s t test or the Mann–Whitney U test was used to compare differences in continuous variables. The Chisquare test or Fisher’s exact test was used to compare categorical variables. To assess cross-sectional relationships between serum potassium and clinical parameters such as age, sex, eGFR, fasting glucose and insulin concentrations, serum bicarbonate concentration, serum aldosterone level, albuminuria, the use of ACEIs or ARBs, the use of aldosterone receptor blockers such as spironolactone, the use of diuretics (loop and/or hydrochlorothiazide), and insulin resistance assessed by HOMA index score, simple linear regression analysis was performed first, after which multiple regression analysis was carried out using a stepwise selection process. The incidence of hyperkalemia during follow-up period was also evaluated. The data including prescription status at the time of the development of hyperkalemia were used for the analysis and comparison between patients with insulin resistance and those without. Variables that can affect potassium concentration such as age, sex, the presence of hypertension and diabetic nephropathy, renal function, drugs (RAAS inhibitors, β-blockers, diuretics and insulin), and insulin resistance were analyzed with logistic regression analysis. Statistical significance was defined as a p value
