Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance.

UNLABELLED: Aims/Introduction: Reduced insulin sensitivity and secretion are important in the pathogenesis of type 2 diabetes. Their relationships to prediabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have been previously studied with the oral glucose tolerance test (OGTT). We investigated whether or not baseline measures of insulin secretion and sensitivity obtained from fasting blood specimens were related to the development of prediabetes and how these measures compared with those based on the OGTT. MATERIALS AND METHODS: In 152 Japanese subjects with normal glucose tolerance, we measured baseline plasma glucose and insulin after an overnight fast and during a 75 g OGTT, insulin resistance index (homeostasis model assessment [HOMA-IR]), and insulin secretion (insulinogenic index [30 min insulin - fasting insulin] ÷ [30 min glucose - fasting glucose] or HOMA-ß). RESULTS: At a 5-6 year (mean 5.7 years) follow-up examination, we confirmed 36 cases of prediabetes. After adjusting for age, sex, family history of diabetes, body mass index, and 2-h plasma glucose, the odds ratio comparing the lowest tertile (≤0.82) of insulinogenic index with the highest tertile (≥1.43) was 6.98 (95% confidence interval, 1.96-24.85) and was 10.72 (2.08-55.3) comparing the lowest tertile (≤76.3) of HOMA-ß with the highest tertile (≥122.1), whereas the respective odds ratios of HOMA-IR were 3.74 (1.03-13.57) and 10.89 (1.93-61.41) comparing the highest tertile (≥1.95) with the lowest tertile (≤1.25). CONCLUSIONS: Lower insulin secretion and sensitivity are independent risk factors for prediabetes. Clinically practical identification of those at risk for prediabetes is obtainable from HOMA-ß and HOMA-IR, both of which are measured in fasting state. (J Diabetes Invest, doi: 10.1111.j.2040-1124.2010.00041.x, 2010).

Isolated hearing loss associated with T7511C mutation in mitochondrial DNA.

CONCLUSION: The T7511C mutation is considered responsible for maternally inherited, isolated sensorineural hearing loss of cochlear origin. This mutation should be screened for in cases of nonsyndromic, familial sensorineural hearing loss compatible with maternal transmission. OBJECTIVES: To clarify the audiovestibular phenotype characteristics associated with a T7511C mutation in mitochondrial DNA and determine whether it causes isolated sensorineural hearing loss unaccompanied by other neuromuscular symptoms or signs. SUBJECTS AND METHODS: A proband and affected members of a Japanese family harboring a T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene were enrolled. Mutation analysis was done on genomic DNA extracted from blood samples. Auditory pathways involved were investigated in examinations that included pure-tone audiograms, acoustic reflexes, speech discrimination testing, distortion-product otoacoustic emissions, and auditory brainstem responses. The presence of other signs and symptoms, including vestibular ones, was investigated. RESULTS: We identified a homoplasmic T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene in this family. No other pathogenic mutations associated with hearing loss or common mitochondrial diseases were found. Hearing loss of cochlear origin mainly developed at mid to high frequencies. Vestibular systems were well preserved. No symptoms or signs characteristic of mitochondrial diseases were present in any family members.

Ototoxicity after use of neomycin eardrops is unrelated to A1555G point mutation in mitochondrial DNA.

Ear drops containing neomycin only rarely cause ototoxicity. The authors report on three patients with a tympanic membrane perforation who developed severe ototoxicity after use of eardrops containing 0.35 per cent neomycin. Mitochondrial DNA analysis revealed that there was no A1555G point mutation in these patients. This finding indicates that application of low concentration neomycin to the middle ear can cause severe inner ear damage even in humans who are not hyper-susceptible to aminoglycosides.

A case showing an association between type 1 diabetes mellitus and Kabuki syndrome.

The case of a 31-year-old female suffering from type 1 diabetes mellitus (DM) and Kabuki syndrome is presented. The patient was diagnosed as having impaired glucose tolerance (IGT) at age 18; secondary amenorrhea occurred at age 20, following acute body weight loss. Extensive examination revealed the patient to have a slowly progressive form of type 1 DM and, based on the physical findings, including her facial features, she was diagnosed as also having congenital Kabuki syndrome. Since then, this patient has experienced several episodes of diabetic ketoacidosis, all of which were brought about by prolonged bronchial infection. Although it is perhaps reasonable at present to consider this case to represent a chance association, further clinical investigations will be carried out to clarify whether or not Kabuki syndrome and type 1 DM have any common pathogenic features.

Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene.

We investigated three families with maternally inherited deafness associated with a 1555 A-to-G substitution in the 12S ribosomal RNA gene. Probands in these families developed deafness following streptomycin treatment, whereas several family members who did not receive aminoglycoside showed onset of deafness in middle age. One proband had a non-synonymous A14062G mutation in the ND5 gene and the other had a non-synonymous G15221A mutation in the cytochrome b gene and a T1391C mutation in the 12S ribosomal RNA gene, whose importance in disease expression remains to be clarified. Two muscle biopsies from the patients with and without streptomycin treatment, showed similar findings; a moth-eaten appearance with decreased cytochrome c oxidase activity and abnormal mitochondrial morphology. These findings suggest that even without exposure to aminoglycoside the A1555G mutation may impair mitochondrial function and that the mitochondrial abnormalities associated with the A1555G mutation may be expressed in tissues other than those of the auditory system.