Secondary oxalosis induced by xylitol concurrent with lithium-induced nephrogenic diabetes insipidus: a case report.

BACKGROUND: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare. CASE PRESENTATION: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission. CONCLUSIONS: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Lower serum calcium levels are a risk factor for a decrease in eGFR in a general non-chronic kidney disease population.

Association between serum calcium (Ca) levels and kidney dysfunction progression in a non-chronic kidney disease (CKD) population has not been well elucidated, especially in consideration for classical metabolic risk conditions such as hypertension, dyslipidemia, and diabetes, and those related to Ca metabolism. Among participants of the population-based Iwaki study of Japanese people, those with an estimated glomerular filtration rate (eGFR) ≧60 ml/min/1.73 m2 and age ≧40 years, and who attended the study consecutively in 2014 and 2015 were enrolled (gender (M/F): 218/380; age: 58.9 ± 10.2). Regression analysis showed a significant correlation between serum Ca levels and a change in eGFR in the 1-year period (∆eGFR) after adjustment with multiple factors including those related to Ca metabolism (ß = 0.184, p < 0.001). When subjects were stratified into tertiles based on their serum Ca levels (higher >9.6 mg/dL, middle 9.4-9.6 mg/dL, lower <9.4 mg/dL), lower serum Ca levels were a significant risk for a rapid decliner of eGFR designated as the lower one third of ∆eGFR (<-4.40 ml/min/1.73 m2) (odds ratio 2.41, 95% confidence interval 1.47-3.94). Lower serum Ca levels are a significant risk for rapid decrease in eGFR, independent of previously reported metabolic risk factors in this general population with non-CKD, or eGFR ≧60 ml/min/1.73 m2.

Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion.

How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-ß). Univariate linear regression analyses showed a correlation between PC2 and HOMA-ß (ß = -0.248, p < 0.0001), but not between PC1 and HOMA-ß (ß = -0.004, p = 0.9048). The correration between PC2 and HOMA-ß persisted after adjustment for multiple factors (ß = -0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-ß (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35-2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.

Association between serum prolactin levels and insulin resistance in non-diabetic men.

Prolactin (PRL) has roles in various physiological functions. Although experimental studies showed that PRL has both beneficial and adverse effects on type 2 diabetes mellitus, clinical findings in subjects with hyperprolactinemia indicate adverse effects on glucose metabolism. However, effects of PRL within the physiological range in human are controversial. A population-based study of 370 Japanese men enrolled in the 2014 Iwaki study (aged 52.0 ± 14.8 years). In this cross-sectional study, associations between serum PRL levels and homeostatic model assessment (HOMA) indices representing glucose metabolism in a physiological setting were examined using multivariable regression analysis. Although univariate linear regression analyses showed significant associations between serum PRL levels and HOMA indices, adjustment with multiple factors made the association with HOMA-ß (insulin secretion) insignificant, while those with HOMA-R (insulin resistance) remained significant (ß = 0.084, p = 0.035). Non-linear regression analyses showed a regression curve with a peak at serum PRL level, 12.4 ng/mL and a positive association of serum PRL level with HOMA-R below the peak (ß = 0.119, p = 0.004). Higher serum PRL levels within the physiological range seem to be associated with insulin resistance in men.

Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population.

Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study. Association between serum cortisol levels and insulin resistance/secretion assessed by homeostasis model assessment using fasting blood glucose and insulin levels (HOMA-R and HOMA-ß, respectively) were examined. Univariate linear regression analyses showed correlation of serum cortisol levels with HOMA-ß (ß = -0.134, p <0.001) but not with HOMA-R (ß = 0.042, p = 0.172). Adjustments for age, gender, and the multiple clinical characteristics correlated with HOMA indices showed similar results (HOMA-ß: ß = -0.062, p = 0.025; HOMA-R: ß = -0.023, p = 0.394). The correlation between serum cortisol levels and HOMA-ß remained significant after adjustment for HOMA- R (ß = -0.057, p = 0.034). When subjects were tertiled based on serum cortisol levels, the highest tertile was at greater risk of decreased insulin secretion (defined as lower one third of HOMA-ß (≤70)) than the lowest tertile, after adjustment for multiple factors including HOMA- R (odds ratio 1.26, 95% confidence interval 1.03-1.54). In conclusion, higher serum cortisol levels are significantly associated with decreased insulin secretion in the physiological cortisol range in a Japanese population.

Association Between Pituitary-Adrenal Axis Dominance Over the Renin-Angiotensin-Aldosterone System and Hypertension.

CONTEXT: The hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin aldosterone system (RAAS) are well known to be associated with hypertension. However, the extent of the effects is not yet well elucidated in general conditions. OBJECTIVE: To separately determine the effect of the HPA axis and the RAAS on hypertension in a general population. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of 859 Japanese individuals enrolled in the 2014 Iwaki study and without hypertension or steroid treatment (age, 50.2 ± 14.7 years). MAIN OUTCOME MEASURES: Hypertension prevalence, plasma concentration of aldosterone, ACTH, cortisol, and plasma renin activity. RESULTS: Principal component (PC) analysis using these four hormones identified two PCs (PC1 and PC2), which represent levels of these hormones as a whole, and dominance between the HPA axis (ACTH and cortisol) and the RAAS (plasma renin activity and plasma concentration of aldosterone), respectively. Association between these PCs and hypertension was significant (PC1, high vs low, odds ratio [OR], 1.48; 95% confidence interval [CI], 1.09-2.02; and PC2, HPA axis vs RAAS dominancy, OR, 2.08; and 95% CI, 1.51-2.85). However, association between the hormone levels as a whole and hypertension became insignificant after adjustment for multiple factors including these PCs together. However, association between the HPA axis dominance and hypertension remained significant even after the adjustment (the HPA axis vs the RAAS, OR, 1.73; 95% CI, 1.20-2.48). CONCLUSIONS: The HPA axis dominance over the RAAS is significantly associated with hypertension in a Japanese population.