[Who should provide diabetes care to elderly diabetic patients in long-term care homes?]

As a result of rapid aging, the number of elderly diabetic patients with decreased self-management ability in Japan is increasing. Currently, family members primarily perform self-injection at home and self-measurement of blood glucose for patients that require these procedures. Patients who cannot receive assistance from family members, will be admitted into long-term care homes. Due to the shortage of nurses in many long-term care homes, the homes can only accept a limited number of diabetic patients with decreased self-management abilities. There are two measures that may be considered: the first is to significantly increase the number of nurses; the second is to delegate diabetes care to non-medical and non-nursing care workers in long-term care homes. However, both options should be carefully considered before making a choice.

Irrational Responses to Risk Preference Questionnaires by Patients with Diabetes with or without Retinopathy and Comparison with Those without Diabetes.

PURPOSE: The risk preferences of patients with diabetes have profound effects on the progression of complications. The present study aimed to clarify whether the preferences of patients with diabetes and retinopathy are deliberately risk-seeking or irrational and whether this propensity is specific to those with retinopathy or is also found in patients without retinopathy compared with those without diabetes. PATIENTS AND METHODS: A total of 394 patients with diabetes (264 without retinopathy and 130 with retinopathy) and 198 patients without diabetes agreed to participate in this survey. The questions were modified versions of those from the Japan Household Survey on Consumer Preferences and Satisfaction, which sought to determine the participants' personal socioeconomic status and risk preferences. In the questionnaires, responses were analyzed by determining the participants' willingness to pay for a lottery ticket and for an insurance policy. Irrational responses were defined as violations of two axioms of the Expected Utility Theory: completeness and transitivity. RESULTS: The incidence of irrational responses increased with age and was associated with educational level. The incidence of irrational responses was significantly higher in patients with retinopathy than in those without retinopathy after adjusting for age and educational level. There was no significant difference in the incidence of irrational responses between patients with diabetes but without retinopathy and those without diabetes. CONCLUSION: The risk-seeking behavior of patients with diabetes and retinopathy was not deliberate but was irrational under uncertainty. Medical professionals should be aware of their patients' propensity to make irrational decisions, which is an important risk factor for the progression of retinopathy in patients with diabetes regardless of age and educational level.

[Who should provide diabetes care to elderly diabetic patients with decreased self-management skills?]

As a result of the rapid aging of society, the number of elderly diabetic patients with a decreased self-management ability in Japan is increasing. At present, family members primarily perform injection at home and measure the blood glucose levels for patients who require these procedures. However, as aging progresses and the birthrate further declines, it is expected that it will become difficult for such patients to receive assistance from their family members. Therefore, a discussion at the national level and development of urgent measures are required. In the future, the expanded involvement of those with medical qualifications and augmented multi-occupational collaboration-specifically, increasing the frequency of visiting nursing services, facilitating injections at home by pharmacists and making the most of "community-based integrated care systems", without major changes in the current legislation, will be foremost in reinforcing or taking the place of family members performing injections at home and measuring blood glucose levels. If cost is given the highest priority, injection at home and measurement of blood glucose levels by non-medical and non-nursing care workers seems to be the best option. However, careful deliberation is required.

Heart Failure with Hyperthyroidism Demonstrating Discrepancy between the Clinical Course and B-type Natriuretic Peptide Levels.

A 35-year-old Japanese man was emergently admitted to our hospital with chief complaints of palpitation and dyspnea. He has been treated for Basedow's disease. He was diagnosed with acute decompensated heart failure, atrial fibrillation and thyrotoxicosis. We started anti-thyroid agents and a treatment for heart failure with beta blockers and diuretics under anti-coagulation therapy. His B-type natriuretic peptide levels remained high, although the heart failure had been compensated and the heart rate was well controlled while hyperthyroidism still existed. We should bear in mind that a discrepancy can exist between the clinical course and the B-type natriuretic peptide level in heart failure patients complicated with hyperthyroidism.

Recovery from exocrine pancreatic insufficiency in a patient with fulminant type 1 diabetes.

A 34-year-old man was admitted to our hospital with diabetic ketoacidosis due to fulminant type 1 diabetes. The patient's pancreatic exocrine and endocrine functions were as follows: the bentiromide (PABA) test value on day 14 was 33.9%, thus indicating exocrine dysfunction. One year and a half later, the PABA test value had improved to 71.0%. On the other hand, the serum C-peptide level after meal ingestion was under the detection limit. The mechanisms underlying pancreatic exocrine abnormalities seem to be different from those underlying accelerated pancreatic beta-cell failure in patients with fulminant type 1 diabetes.

Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia.

Oncogenic osteomalacia (OOM), or tumor-induced osteomalacia, is a rare disease characterized by renal phosphate wasting and osteomalacia. It arises due to the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Matrix extracellular phosphoglycoprotein (MEPE) is predominantly expressed in odontoblasts, osteoblasts, and osteocytes. Although the presence of MEPE mRNA has been reported in some OOM tumors, little is known about the prevalence of MEPE expression in OOM tumors. In this study, the expression of MEPE and FGF-23 in OOM tumors was investigated at the transcriptional and translational levels. Eleven causative OOM tumors were analyzed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry for MEPE and FGF-23 expression. Hemangiopericytomas and giant cell tumors, pathological diagnoses that are common in cases of OOM, were obtained from non-osteomalacic patients and analyzed as controls. The gene expression level of FGF23 and MEPE in OOM tumors was 10(4)- and 10(5)-times higher, respectively, than in non-OOM tumors. Immunohistochemical staining revealed that FGF-23 protein was expressed in all OOM tumors, and MEPE was expressed in 10 out of 11 OOM tumors. Thus, MEPE expression was common in OOM tumors, similar to FGF-23. These results indicate that, in addition to the hypophosphatemic effects of FGF-23, MEPE or the MEPE-derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute to decreased bone mineralization in OOM patients.

Comparison of effects of azelnidipine and trichlormethiazide in combination with olmesartan on blood pressure and metabolic parameters in hypertensive type 2 diabetic patients.

UNLABELLED: Aims/Introduction: Angiotensin II type 1 receptor blockers (ARB) are regarded as first-line treatment for type 2 diabetes with hypertension. However, lowering blood pressure to the target level often requires more than one antihypertensive agent as recommended by the guideline. In this open-label, prospective, crossover clinical trial, we compared the effects of combination treatment of ARB with a calcium channel blocker (CCB) or with a low-dose thiazide diuretic on blood pressure (BP) and various metabolic parameters in hypertensive patients with type 2 diabetes. MATERIALS AND METHODS: A total of 39 Japanese type 2 diabetics with hypertension treated with olmesartan (20 mg/day) for at least 8 weeks were recruited to this study. At study entry, treatment was switched to either olmesartan (20 mg/day)/azelnidipine (16 mg/day) or olmesartan (20 mg/day)/trichlormethiazide (1 mg/day) and continued for 12 weeks. Then, the drugs were switched and treatment was continued for another 12 weeks. We measured clinical blood pressure and various metabolic parameters before and at the end of each study arm. RESULTS: Compared with the olmesartan/trichlormethiazide treatment, treatment with olmesartan/azelnidipine achieved superior clinical blood pressure and pulse rate control. In contrast, the treatment with olmesartan/trichlormethiazide resulted in increased HbA1c, serum uric acid and worsening of estimated glomerular filtration rate, though there were no differences in other metabolic parameters including urine 8-hydroxy-2'-deoxyguanosine, C-reactive protein and adiponectin between the two treatments. CONCLUSIONS: Our results show that the combination of ARB with azelnidipine is more beneficial with regard to blood pressure control and metabolic outcome than the combination of olmesartan with low dose trichlormethiazide. This trial was registered with UMIN clinical trial registry (no. UMIN000005064). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00135.x, 2011).

Fulminant emphysematous pyelonephritis (EPN) in a diabetic patient suspected of having multiple tumors.

Multiple tumors in the liver, kidney, and on the posterior side of the urinary bladder were accidentally found when a diabetic woman visited the hospital. She refused to undergo surgery; therefore, she was only observed for 2 months. Subsequently, she was found unconscious at home and diagnosed with urinary infection, sepsis, and hyperglycemic hyperosmolar non-ketotic coma. The case followed a fulminant course, and she soon died. Postmortem computed tomography revealed emphysematous pyelonephritis (EPN), a rare, life-threatening infection. This case highlights the importance of carefully managing infection in diabetic patients, and it may contribute to clarifying the pathogenesis of EPN.

The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels.

Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.

Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.

Fibrous dysplasia (FD) patients sometimes suffer from concomitant hypophosphatemic rickets/osteomalacia, resulting from renal phosphate wasting. It was recently reported that FD tissue in the patients with McCune-Albright syndrome (MAS) expressed fibroblast growth factor-23 (FGF-23), which is now known to be as a pathogenic phosphaturic factor in patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets. Since it remains controversial whether serum phosphate levels are influenced by FGF23 expressions in FD tissue, isolated FD patients without MAS syndrome were examined for the relationship between FGF23 expressions, circulating levels of FGF-23 and phosphate to negate the effects of MAS-associated endocrine abnormalities on serum phosphate. Eighteen paraffin embedded FD tissues and 2 frozen tissues were obtained for the study. Sixteen of 18 isolated FD tissues were successfully analyzed GNAS gene, which exhibited activated mutations observed in MAS. Eight of 16 FD tissues, which exhibited GNAS mutations, revealed positive staining for FGF-23. These evidence indicate that postzygotic activated mutations of GNAS is necessary for the FD tissue formation by mosaic distribution of mutated osteogenic cell lineage, but is not sufficient to elevate FGF23 expression causing generalized osteomalacia with severe renal phosphate wasting. The expression level of FGF23 in isolated FD tissue with hypophosphatemic osteomalacia determined by real-time PCR was abundant close to the levels in OOM tumors. Osteoblasts/osteocytes in woven bone were predominant source of circulating FGF-23 in FD tissues by immunohistochemistry. A negative correlation of the intensity of FGF-23 staining with serum inorganic phosphate levels indicated that the expression of FGF23 in focal FD tissues could be a prominent determinant of serum phosphate levels in isolated FD patient. These data provide novel insights into the regulatory mechanism of serum inorganic phosphate levels in isolated FD patients and extend the notion that FGF-23 originating from FD tissue may cause hypophosphatemia not only in isolated FD patients but also in the patients with MAS syndrome.