Determinación niveles de glucosa por medio de espectroscopía como método no invasivo / Determination of glucose levels by means of spectroscopy as a non-invasive method

Introducción: la diabetes mellitus es uno de los problemas más graves de salud pública que enfrenta México. El factor más preocupante es la falta de control de la misma, lo que incide de manera directa, causando daños severos a la salud y la calidad de vida del paciente y familiares, así como una carga económica al país. Por lo tanto, el desarrollo de un método no invasivo para la medición de la glucemia proporcionaría a los pacientes una forma sencilla e indolora de monitoreo y, en consecuencia, un mejor control de la diabetes. Objetivo: investigar, desarrollar y validar un sensor no invasivo por medio de la espectroscopía para la estimación del nivel de glucosa en sangre. Material y métodos: se realizó un análisis de estudio transversal analítico de correlación realizado en las instalaciones del laboratorio de la UMAE No 1, Bajío. Se incluyeron pacientes adultos voluntarios que acudieron al laboratorio de dicha unidad para la toma de niveles de glucosa sérica y de manera simultánea se realizó la medición a través de método no invasivo por espectroscopía y, posteriormente, se compararon ambos resultados para demostrar la validez del dispositivo. Resultados: mediante el análisis de la diferencia de medias de Bland-Altman, se identificó que solamente un paciente tuvo un valor extremo, y que el método para medir la glucosa de manera no invasiva sobreestima hasta un 10.2% del valor de glucosa central. Conclusión: comparando dichos resultados con las normas para glucómetros digitales se concluye que nuestro dispositivo es capaz de proporcionar niveles de glucosa certeros.

Background: Diabetes mellitus is one of the most serious public health problems in Mexico. The most worrying factor is the lack of control of it, which has a direct impact, causing severe damage to the health and quality of life of the patient and its family, as well as an economic burden to the health system. Therefore, the development of a non-invasive method for measuring blood glucose would provide to patients a simple and painless way of monitoring and consequently better control of diabetes. Objective: Research, development and validation of a non-invasive sensor by means of spectroscopy for the estimation of the blood glucose level. Material and methods: An analysis of a cross-sectional analytical correlation study was carried out in the facilities of the laboratory at the UMAE No. 1, Bajío. Voluntary adult patients who attended the laboratory of the UMAE to take serum glucose levels were included, and simultaneously the measurement was carried out through a non-invasive method by spectroscopy and, later, both results were compared to demonstrate the validity of the device. Results: By the Bland-Altman mean difference analysis, it was identified that only one patient had an extreme value, and that the method to measure glucose non-invasively overestimates up to 10.2% of the central glucose value. Conclusion: Comparing these results with the standards for digital glucometers, it is concluded that our device is capable of providing accurate glucose levels.

Modifications of adrenal gland ultrastructure in streptozotocin-induced diabetic model rats / Modificaciones de la ultraestructura de la glándula suprarrenal en ratas modelo diabéticas inducidas por estreptozotocina

SUMMARY: The adrenal gland has been associated with the development of classical symptoms in diabetes mellitus (DM), including intensive polyuria and hyperglycemia. During DM, there are hormonal changes in the adrenal gland. Ultrastructural changes of adrenocortical and adrenal medulla cells and their effects on adrenocorticomedullary interaction have not been fully investigated. This study evaluated adrenocortical and adrenal medullary cells and adrenocorticomedullary interactions at ultrastructural levels in a streptozotocin-induced DM model, using transmission electron microscopy. Fifteen male, Sprague-Dawley rats were divided into diabetic model (n = 10) and control (n = 5) groups. Rats were sacrificed at four weeks after induction. The nuclei of some diabetic cortical cells were found to be irregularly shaped. In the cytoplasm, increased numbers of mitochondria and dilated smooth endoplasmic reticulum were observed. However, lipid droplets decreased in the DM model animals. The filopodia of diabetic cortical cells extended to contact the fenestrated capillary and other cortical cells and losses of gap junctions were also observed. Alterations of diabetic chromaffin cells resulted in similar appearances, consisting of irregularly shaped nuclei, swollen mitochondria, distended rough endoplasmic reticulum, and disrupted chromaffin vesicles. Examining adrenocorticomedullary interactions showed that the diabetic cortical chromaffin cells resembled those in the medulla. In the DM model group, collagen fibril depositions were observed between adrenal cells, especially near cell interactions. The filopodia of diabetic cortical cells were larger than those observed for diabetic adrenocorticomedullary interactions and adrenal cortex. These adrenal gland ultrastructural modifications represent contributions to the basic knowledge necessary for investigations of adrenal gland impairment during the early diagnosis of DM patients.

RESUMEN: La glándula suprarrenal se ha asociado con el desarrollo de síntomas clásicos en la diabetes mellitus (DM), que incluyen poliuria intensiva e hiperglucemia. Durante la DM, hay cambios hormonales en la glándula suprarrenal. Los cambios ultraestructurales de las células adrenocorticales y de la médula suprarrenal y sus efectos sobre la interacción adrenocorticomedular no se han investigado completamente. Este estudio evaluó las células adrenocorticales y de la médula suprarrenal y las interacciones adrenocorticomedulares a niveles ultraestructurales en un modelo de DM inducida por estreptozotocina, utilizando microscopía elec- trónica de transmisión. Se dividieron quince ratas macho Sprague- Dawley en grupos de modelo diabético (n = 10) y de control (n = 5). Las ratas se sacrificaron cuatro semanas después de la inducción. Se encontró que los núcleos de algunas células corticales diabéticas tenían una forma irregular. En el citoplasma, se observó un mayor número de mitocondrias y retículo endoplásmico liso dilatado. Sin embargo, las gotitas de lípidos disminuyeron en los animales modelo DM. Los filopodios de las células corticales diabéticas se extendieron para entrar en contacto con el capilar fenestrado y otras células corticales y también se observaron pérdidas de uniones gap. Las alteraciones de las células cromafines diabéticas dieron como resultado apariencias similares, que consistían en núcleos de forma irregular, mitocondrias inflamadas, retículo endoplásmico rugoso distendido y vesículas cromafines rotas. El examen de las interacciones adrenocorticomedulares mostró que las células cromafines corticales diabéticos se parecían a las de la médula. En el grupo del modelo de DM, se observaron depósitos de fibrillas de colágeno entre las células suprarrenales, especialmente cerca de las interacciones celulares. Los filopodios de las células corticales diabéticas eran más grandes que los observados para las interacciones adrenocorticomedulares diabéticas y la corteza suprarrenal. Estas modificaciones ultraestructurales de la glándula suprarrenal contribuyen al conocimiento básico para las investigaciones referente al deterioro de la glándula en el diagnóstico temprano de pacientes con DM.

Cerebellar synaptopathy in streptozotocin-induced diabetic rats / Sinaptopatía cerebelosa en ratas diabéticas inducidas por estreptozotocina

SUMMARY: There is an increasing amount of evidence that supports the diabetic complications of the central nervous system structure and function. The cerebellum, which is one of the primary structure derived from the hindbrain, plays an important role in motor control, motor coordination, and non-motor functions, such as cognitive processing. The synapse is a critical structure that regulates neuronal communication, and well-defined afferent and efferent fibre connections in the cerebellum help in maintaining the proper working order. Thus, the present study sought to investigate the long-term effects of diabetes-induced synaptopathy in the cerebellum, using both histological and ultrastructural studies. Twenty Sprague-Dawley male rats were divided randomly into control and diabetic groups, and diabetes was then induced through a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Six month later, the rats were sacrificed and the cerebellum was removed. Light and electron microscopic examinations showed a degeneration of Purkinje cells (Neuron purkinjense) with shrunken cells, pyknotic nuclei, and synaptopathy, including the reduction in synapse density, number of synaptic vesicles, and maturation of synapses in the molecular layer of diabetic cerebellum. The disruptions in synaptic profiles, which observed in the diabetic condition, could be related to cerebellar dysfunction, thus leading to the defects in coordinated movement, balance, as well as cognitive learning and memory.

RESUMEN: Actualmente existe una creciente evidencia que apoya las complicaciones diabéticas de la estructura y función del sistema nervioso central. El cerebelo, una de las estructuras primarias del cerebro posterior, desempeña un papel importante en el control motor, la coordinación motora y las funciones no motoras, tanto como en el procesamiento cognitivo. La sinapsis es una estructura crítica que regula la comunicación neuronal y las conexiones de fibras aferentes y eferentes bien definidas en el cerebelo, ayudan a mantener el funcionamiento correcto. Por lo tanto, en el presente estudio se investigaron los efectos a largo plazo de la sinaptopatía inducida por la diabetes en el cerebelo, utilizando estudios histológicos y ultraestructurales. Veinte ratas SpragueDawley macho se dividieron al azar en grupos de control y diabetes, se indujó la diabetes a través de una inyección intraperitoneal única de estreptozotocina (60 mg / kg de peso corporal). Seis meses después, se sacrificaron las ratas y se extrajo el cerebelo. Los exámenes de microscopías óptica y electrónica mostraron una degeneración de las neuronas purkinjenses (células de Purkinje), con células reducidas, núcleos picnóticos y sinaptopatía, como también la densidad reducida de sinapsis, el número de vesículas sinápticas y la maduración de las sinapsis en la capa molecular del cerebelo de las ratas diabéticas. Las interrupciones en los perfiles sinápticos, que se observaron en la condición diabética, podrían estar relacionadas con la disfunción cerebelosa, lo que lleva a defectos en el movimiento coordinado, el equilibrio, así como al aprendizaje cognitivo y la memoria.

A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor

We aimed to identify the clinical variables associated with a better glucose-lowering response to the sodium glucose cotransporter 2 inhibitor ipragliflozin in people with type 2 diabetes mellitus (T2DM). We especially focused on urinary glucose excretion (UGE). This was a single-arm multicenter prospective study. A total of 92 people with T2DM aged 20 to 70 years with glycosylated hemoglobin (HbA1c) levels ≥7.0% and ≤9.5% were enrolled. Ipragliflozin (50 mg) was added to the background therapy for these people for 12 weeks. After 3 months treatment with ipragliflozin, the mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of the people reached the HbA1c target of less than 7.0% (P<0.001). In addition, body weight, blood pressure, and lipid parameters were improved after ipragliflozin treatment (all P<0.001). The baseline HbA1c (r=0.66, P<0.001) and morning spot urine glucose to creatinine ratio (r=−0.30, P=0.001) were independently associated with the HbA1c reduction. Ipragliflozin treatment for 12 weeks improves glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicts a better glucose-lowering efficacy of ipragliflozin.

Acute kidney injury associated with Yersinia pseudotuberculosis infection: Forgotten but not gone

BACKGROUND: Yersinia pseudotuberculosis is known to cause fever, gastroenteritis, or acute kidney injury (AKI). There have been several Y. pseudotuberculosis infection outbreaks to date associated with ingestion of contaminated food or unsterile water. While this disease was considered to have practically been eradicated with the improvement in public health, we encountered several cases of AKI associated with Yersinia infection. METHODS: We retrospectively collected data from medical records of patients with suspected Y. pseudotuberculosis infection who visited Seoul National University Children’s Hospital in 2017. RESULTS: There were nine suspected cases of Yersinia infection (six males and three females; age range 2.99–12.18 years). Among them, five cases occurred in May, and seven patients were residing in the metropolitan Seoul area. Three patients had history of drinking mountain water. Every patient first presented with fever for a median of 13 days, followed by gastrointestinal symptoms and oliguria. Imaging studies revealed mesenteric lymphadenitis, terminal ileum wall thickening, and increased renal parenchymal echogenicity. Creatinine levels increased to 5.72 ± 2.18 mg/dL. Urinalysis revealed sterile pyuria, proteinuria, and glycosuria. Oliguria continued for 4 to 17 days, and two patients required dialysis; however, all of them recovered from AKI. Mucocutaneous manifestations developed later. In the diagnostic work-up, Yersinia was isolated from the stool culture in one patient. Anti-Yersinia immunoglobulin (Ig) A and IgG were positive in 6 patients. CONCLUSION: Y. pseudotuberculosis infection is an infrequent cause of interstitial nephritis presenting with AKI. When a patient presents with fever, gastroenteritis, and AKI not resolving despite hydration, the clinician should suspect Y. pseudotuberculosis infection.

Prevalência de indivíduos com alto risco para diabetes atendidos pelo Laboratório de Análises Clínicas da Fundação Universidade Regional de Blumenau / Prevalence of high-risk individuals for diabetes attended by the Laboratory of Clinical Analyzes of the Blumenau Regional University Foundation

Objetivo: Este trabalho tem como objetivo analisar a prevalência de pacientes diabéticos atendimentos no Laboratório de Análises Clínicas da FURB (LAC-FURB), no ano 2015. Métodos: Análise estatística dos dados dos pacientes que realizaram glicemia de jejum e hemoglobina glicada. Foram analisados também os parciais de urina realizados no mesmo dia dos exames plasmáticos, citados anteriormente. Os pacientes apresentavam idade do 0 aos 93 anos com idade média de 46 anos. A coleta dos dados foi realizada no banco de dados do LAC-FURB. Foram excluídos das análises os dados das gestantes pelo diagnóstico diferenciado e os exames de teste de tolerância oral a glicose devido ao pequeno tamanho amostral. Resultados: Foram atendidos no ano de 2015 no LAC-FURB 929 pacientes dos quais 689 realizaram os exames de glicemia de jejum e/ou hemoglobina glicada. De acordo com a análise estatística concluiu-se que 13% dos pacientes tiveram resultados compatíveis com Diabetes mellitus (DM) e 23% foram considerados intolerantes à glicose. Além disso, observou-se que existe uma forte correlação entre os resultados de glicose plasmática de jejum elevada e de hemoglobina glicada, também elevada, assim como os pacientes que apresentaram níveis sanguíneos de glicose acima de 180 mg/dL apresentaram glicosúria. Conclusão: A DM é uma doença complexa que requer inúmeros cuidados e acompanhamento. A análise dos dados evidenciou que 13% dos pacientes tiveram resultados compatíveis com DM e 23% foram considerados intolerantes à glicose, sendo que a maioria dos pacientes diagnosticados foram mulheres. Fatores como o climatério associados com a cultura de maior preocupação e procura por serviços de saúde deste público explicam estes resultados.

Comparação entre três métodos para detecção de glicosúria em cães e gatos / Comparison between three methods for detection of glycosuria in dogs and cats

Objetivo: Objetivou-se nesse estudo avaliar a presença de glicose na urina utilizando três metodologias. Métodos: Foram utilizadas 22 amostras de urina da rotina laboratorial, provenientes de 12 caninos e 10 felinos. As amostras foram submetidas a avaliação da glicosúria através de tiras reagentes urinárias ­ uma com leitura manual e outra automática ­ e reação de Benedict. Aplicou-se o teste de correlação de Pearson para se compararem os resultados entre os métodos. Resultados: A correlação entre os dois tipos de leituras de tiras reagentes foi alta (R=0,80), indicando que os resultados foram semelhantes entre as tiras, e baixa correlação entre ambas as tiras e o teste de Benedict (manual: R=0,35; automática: R=0,44), indicando que os resultados obtidos entre as tiras e o teste de Benedict não foram semelhantes. Conclusão: Os resultados permitem concluir que, assim como em humanos, o teste de Benedict é mais eficiente do que as tiras reagentes na detecção de glicosúria em cães e gatos, já que detectou um maior número de animais com glicosúria do que as tiras reagentes.

Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy

BACKGROUND/AIMS: This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN). METHODS: After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis. RESULTS: Proteinuria, glycosuria, and increased fractional excretion of sodium and K were prominent in groups III and IV (p < 0.05). Diffuse swelling and poor staining of collecting duct epithelial cells were evident in the medullas of group II. Typical lesions of toxic acute tubular injury were prominent in the cortices of groups III and IV. Α-Smooth muscle actin (α-SMA) was higher in the cortices of the mice in groups III and IV versus group II (p < 0.05), and higher in the medullas of group IV than groups I and III (p < 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p < 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p < 0.05), particularly in the case of group II. CONCLUSIONS: AA-I can induce acquired Fanconi syndrome in the acute stage of AAN. Macrophages appear to play a key role in the pathogenesis of AAN and hypokalemic nephropathy. It remains uncertain whether hypokalemia plays any role in AAN and hypokalemia.

Tenofovir-induced renal tubular dysfunction among human immunodeficiency virus patients on antiretroviral therapy in Nigeria: Prospects for early detection of presymptomatic nephrotoxicity

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is relatively safe, although renal toxicity has been reported. In Nigeria, there is insufficient data on renal toxicity among patients on TDF. This study assesses TDF-associated tubular dysfunction among human immunodeficiency virus (HIV) patients at a hospital in Nigeria. METHODS: In this cohort study, 104 adult HIV patients were recruited with a simple random technique from the outpatient clinic. Biochemical indices of renal function were estimated from serum and urine at the 16th and 24th week after an initial assessment at baseline. RESULTS: There were no significant differences in baseline proteinuria or glycosuria between TDF and non-TDF groups. Mean baseline urine and serum parameters did not differ significantly between the two groups (P > 0.05). In the TDF group, all urine parameters differed significantly between baseline and 24th week values (P < 0.001). After 16 weeks, mean urine phosphate and urine uric acid increased significantly (P < 0.05) by 2.97 mg/dL and 50.9 mg/dL, respectively, in the TDF group. The rise in mean urine glucose from baseline to the 24th week was more marked in the TDF than the non-TDF group (0.25 vs. 0.07 mmol/L). Higher mean differences in urine albumin were also recorded in the TDF group from baseline to the 24th week. CONCLUSION: Indicators of tubular dysfunction were markedly higher among patients on the TDF-based treatment regimen. Biomarkers of tubular dysfunction could be useful for detecting pre-symptomatic nephrotoxicity before marked reduction of glomerular filtration rate in HIV patients on TDF.

Adefovir-induced Fanconi syndrome associated with osteomalacia

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Manejo del control glucémico: objetivos de tratamiento y métodos. Hemoglobina glicosilada A1C (HbA1c). Fructosamina. Automonitoreo glucémico. Glucosuria. Cetonuria / Management of glycemia monitoring: objectives of treatment and methods. Glycosilated hemoglobin A1c (HbA1c). Fructosamine. Self-blood glucose monitoring. Glycosuria. Ketonuria

En la medición estándar del control y el seguimiento en pacientes con diabetes, la hemoglobina glicosilada (HbA1C) presenta dificultades en la insuficiencia renal, en la cual puede no ser buen indicador del control glucémico. La fructosamina no es válida cuando la albumina es menor a 3 mg/dl, mientras que la glucosuria y la cetonuria no son herramientas de medición efectiva en enfermedad renal. El automonitoreo glucémico (AMG) individualizado es un método útil en todos los estadios renales y el de mayor valor en el control y seguimiento en insuficiencia renal avanzada y tratamientos renales sustitutivos

A Case of Isolated Glycosuria Mediated by an SLC5A2 Gene Mutation and Characterized by Postprandial Heavy Glycosuria Without Salt Wasting

Familial renal glycosuria (FRG) is an inherited disorder characterized by persistent glycosuria in the absence of hyperglycemia. It is caused by mutations in the sodium-glucose co-transporter, leading to increase in the renal excretion of glucose and sodium. However, there have been no studies on the role of fasting and postprandial changes in the urinary sodium excretion in patients with FRG. We report a case of renal glycosuria, which was confirmed by a SLC5A2 mutation via gene sequencing, and compared the postprandial urinary glucose and sodium excretion. A 26-year-old man sometimes experienced glycosuria on routine screening; however, other laboratory findings were normal. His fasting and postprandial urinary glucose excretion levels were 295mg/dL and 2,170mg/dL, respectively. The fasting and postprandial urinary sodium excretion levels were 200mEq/L and 89mEq/L, respectively. In patients with FRG, excessive diuresis might be prevented by a compensatory mechanism that reduces postprandial sodium excretion.

Fanconi Syndrome Associated with Long-term Adefovir and Subsequent Tenofovir Therapy for Chronic Hepatitis B Infection / 대한내과학회지

Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogues used to treat chronic hepatitis B (CHB) infection. Nephrotoxicity associated with the use of these medications causes Fanconi syndrome, a rare condition involving generalized dysfunction of the proximal renal tubule causing impaired reabsorption of glucose, uric acid, and phosphate. Fanconi syndrome has been previously reported in patients with human immunodeficiency virus (HIV) or HIV-CHB coinfection treated with other antiretroviral therapies. However, it is rarely reported in patients with CHB monoinfection. We observed a case of Fanconi syndrome in a 61-year-old woman with CHB monoinfection and a history of long-term ADV therapy (42 months), followed by TDF treatment for 9 months. She presented with ankle pain and a tingling sensation in both lower extremities. Laboratory tests revealed hypokalemia, hypocalcemia, hypophosphatemia, hypouricemia, proteinuria, and glycosuria. This case illustrates the importance of recognizing Fanconi syndrome associated with nucleotide analogue treatment and the need to carefully observe symptoms and monitor renal function in these patients.

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. RESULTS: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. CONCLUSIONS: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification. .

Serum uric acid and disorders of glucose metabolism: the role of glycosuria

Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

A case of Fanconi syndrome accompanied by crystal depositions in tubular cells in a patient with multiple myeloma

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

An Unusual Presentation of Diabetic Ketoacidosis in Familial Hajdu-Cheney Syndrome: A Case Report

A 21-year-old man with diabetic ketoacidosis (DKA) displayed short and clubbed fingers and marked eyebrow, which are typical of Hajdu-Cheney Syndrome (HCS). Laboratory findings confirmed type 1 diabetes mellitus (DM). After conservative care with hydration and insulin supply, metabolic impairment was improved. Examinations of bone and metabolism revealed osteoporosis and craniofacial abnormalities. The mutation (c.6443T>G) of the NOTCH2 gene was found. The patient was diagnosed with HCS and DM. There may be a relationship between HCS and DM, with development of pancreatic symptoms related to the NOTCH2 gene mutation.

Evaluation of the Clinical Significance of Ketonuria

BACKGROUND: Urine ketone test is commonly used to screen for diabetic ketoacidosis (DKA). Ketonuria also develops in patients with disease conditions other than DKA. However, the prevalence of DKA in patients with ketonuria is not known. We investigated the prevalence of ketonuria and characteristics of patients with ketonuria and estimated the prevalence of DKA among them to study the clinical significance of ketonuria as an indicator of DKA. METHODS: We studied 1,314 adult and 1,027 pediatric patients who underwent urinalysis. The prevalence of ketonuria in the different groups of patients, classified according to the types of their visits to the institution, was investigated, and the relationships between ketonuria and albuminuria, glycosuria, and bilirubinuria were evaluated. RESULTS: The overall prevalence of ketonuria was 9.1%. The prevalences of ketonuria in adult and pediatric patients were 4.3% and 15.2%, respectively. The prevalences of ketonuria were the highest in the adult (9.7%) and pediatric (28%) patients in the group that had visited the emergency department. Among patients with ketonuria, 7% adult and 3.8% pediatric patients showed glycosuria. CONCLUSIONS: This study showed that the prevalence of DKA in patients with ketonuria, defined as the simultaneous presence of ketone bodies and glucose in urine, was only 7%. Therefore, we concluded that ketonuria might be clinically significant as an indicator of acute or severe disease status rather than of DKA.

Ifosfamide nephropathy in patients with sarcoma

Ifosfamide is an alkylating agent, frequently used in the treatment of sarcoma. Major side effects of ifosfamide are classified as nephropathy, neuropathy, and hematologic complications. The aim of present study was to determine the frequency and severity of ifosfamide nephropathy in patients with various types of sarcoma. Ninety patients [52 males and 38 females] who had received ifosfamide chemotherapy for sarcoma were included in this study. Data on physical examination, laboratory studies, and estimation of glomerular filtration rate were collected. The median duration of follow-up was 6 to 12 months. Records of documented nephropathy were identified in these patients. The age range of patients on ifosfamide was 5 to 59 years. Thirty-four of the patients were children and 56 were adults. The most common renal side effects were proteinuria [15.5%], glycosuria [7.8%], elevation of serum creatinine [2.2%], hematuria [14.4%], and combination of proteinuria and glycosuria [5.5%]. None of the patients had gross hematuria, but microscopic hematuria was present in 14.4%. Ifosfamide nephropathy was seen with different degrees of severity in patients with sarcoma. Monitoring of the side effects of ifosfamide should be revised in different populations