Sodium-Glucose Cotransporter-2 Inhibitors: Lack of a Complete History Delays Diagnosis.

On 15 May 2015, the U.S. Food and Drug Administration (FDA) warned that administration of sodium-glucose cotransporter-2 (SGLT2) inhibitors could lead to ketoacidosis in patients with diabetes mellitus. This announcement came more than 2 years after the FDA's first approval of an SGLT2 inhibitor, although the phenomenon had been known for more than 125 years. Luminaries of diabetes research (including Josef von Mering, Frederick Allen, I. Arthur Mirsky, and George Cahill) had described ketosis and ketoacidosis induced by administration of the phytochemical phlorizin, the prototypical SGLT inhibitor, as well as in patients with familial renal glucosuria, a condition that is considered a natural model of SGLT2 inhibition. Neither government regulators nor manufacturers of SGLT2 inhibitors evinced an awareness of this extensive historical record. The absence of historical inquiry delayed notice of ketoacidosis as an adverse reaction, which could have reduced the burden of illness from these drugs.

Nefritis del túbulo intersticial y uveítis con síndrome de Fanconi / Tubulo-interstitial nephritis and uveitis with Fanconi syndrome

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Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.

BACKGROUND: The best described primary inherited proximal tubulopathies include X-linked hypercalciuric nephrolithiasis (XLHN), caused by a mutation in the chloride channel gene CLCN5, and classic Fanconi's syndrome, the genetic basis of which is unknown. The aim of this study is to examine the clinical, biochemical, and genetic characteristics of a highly consanguineous Druze family with autosomal recessive proximal tubulopathy and hypercalciuria (ARPTH), a syndrome not reported previously. METHODS: Three children (2 girls, 1 boy) of the family referred for evaluation of renal glycosuria and hypercalciuria and 10 of their close relatives were evaluated clinically and biochemically. All study participants underwent genetic analysis to exclude involvement of the CLCN5 gene. RESULTS: Evaluation of the 3 affected children showed glycosuria, generalized aminoaciduria, hypouricemia, uricosuria, low molecular weight (LMW) proteinuria, and hypercalciuria in all 3 children and phosphaturia in 2 children. They had no metabolic acidosis or renal insufficiency. One affected girl had nephrocalcinosis. Two children had a history of growth retardation and radiological findings of metabolic bone disease. Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH)2Vit D] blood levels in affected children were normal. Unaffected family members examined had no renal tubular defects or LMW proteinuria. Genetic linkage analysis excluded cosegregation of the ARPTH phenotype with the CLCN5 locus. CONCLUSION: ARPTH is a new syndrome characterized by nonacidotic proximal tubulopathy, hypercalciuria, metabolic bone disease, and growth retardation. It can be distinguished from XLHN by its autosomal recessive mode of inheritance and normal serum levels of calciotropic hormones, as well as the absence of LMW proteinuria in obligate carriers. The gene mutated in ARPTH remains to be identified.

Diabetes mortality in persons under 45 years of age.

A detailed review of death certificates in Washington State for the years 1968-1979 was undertaken to analyze diabetes mortality for persons under 45 years of age. Diabetics in this age group had a mortality rate from medical causes eight times higher than that of the comparable general population. Almost one-third of the deaths were due to acute complications for which there is definitive medical therapy. Over the 12-year period there was no consistent decline in mortality rates or in deaths from acute complications, nor was there evidence of increased survivorship as reflected in the average age at death. Although residence in areas of sparse medical resources was not associated with high mortality rates, a significant proportion of deaths in all geographical areas occurred at home or before arrival at a hospital. Mortality rates and the proportion of deaths from acute, potentially preventable causes were higher in this study than in other recently published series, suggesting that early diabetes mortality may be a more serious problem than has been previously recognized. Diabetes mortality in this age group can be considered a "sentinel health event" and should call attention to potential problems in health care delivery.

Glycosylated hemoglobins and diabetes mellitus.

Glycosylated hemoglobins result from post-translational changes in the hemoglobin molecule, and their levels correlate well with glycemic levels over the previous six to 10 weeks. Their use as an aid in monitoring diabetic control appears to be well established, but their value in predicting complications of diabetes and in diagnosing milder forms of diabetes is as yet unknown. Of the numerous methods available for the analysis of glycosylated hemoglobins, none has been evaluated extensively in a routine laboratory setting. However, liquid chromatography, isoelectric focusing, and radioimmunoassay techniques all give adequate results. For the purposes of monitoring long term diabetic control, assay of the fast hemoglobin fraction (AIa+b+c) appears adequate. However, for investigative purposes, when optimal sensitivity may be required, specific measurement of hemoglobin AIc is recommended.

Ten-year follow-up report on Birmingham Diabetes Survey of 1961. Report by the Birmingham Diabetes Survey Working Party.

In a diabetes survey in 1960-1, 808 patients from a whole-practice population who either had glycosuria or were used as age- and sex-matched controls were given a 50-g oral glucose tolerance test (GTT). Ten years later the test was repeated in 382 cases. Of the original group, 126 had died and a similar number refused the second test. The original GTT results were classed as normal or as showing GTT diabetes, lag storage, renal glycosuria, or miscellaneous abnormalities. Most of those who converted to florid diabetes came from the GTT diabetes group, all the remainder having shown another minor degree of abnormality in the test; 23% with GTT diabetes, however, remained unchanged, while 32% returned to normal or had only minor anomalies. Of the original lag-storage group 57% remained unchanged or became normal, though 24% had converted to a diabetic abnormality. Renal glycosuria was an innocent peculiarity. The various miscellaneous abnormalities tended to change and showed an excessive conversion to diabetes. There was no accelerating trend towards diabetes in the second five years of follow-up. Those who developed florid diabetes showed an excess mortality comparable to that of clinical diabetics in general. Those who remained normal had the lowest mortality, while those with minor abnormalities occupied an intermediate position.