Erratum: Correction of Figure. Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma.

This corrects the article on p. 498 in vol. 29, PMID: 25325272.

Influence of the definition of "metabolically healthy obesity" on the progression of coronary artery calcification.

OBJECTIVES: Debates whether metabolically healthy obesity (MHO) increases the cardiovascular risk might be due to the metabolic instability of MHO or the absence of a perfect definition of MHO. Therefore, we aimed to investigate the influence of the MHO phenotype on the coronary artery calcium score (CACS) progression according to definition of MHO. METHODS: We analyzed a retrospective cohort with a CACS of 0 at baseline and available serial CACS measurements taken ≥ 12 months apart (n = 1,218). Obesity was defined as BMI ≥ 25 kg/m2, and MHO was defined as obesity accompanied by ≤ 1 (MHO class I) or 0 (MHO class II) components of metabolic syndrome (MetS). RESULTS: During a median follow-up of 45 months, 32.2% of MHO class I and 10.2% of MHO class II subjects developed MetS. Compared to non-obese/metabolically healthy subjects (reference group), hazard ratios (HR) for development of MetS were 2.174 (95% confidence interval [CI]: 1.513-3.124) and 1.166 (95% CI: 0.434-3.129) for MHO class I and II subjects, respectively. The MHO class I subjects showed a significantly increased risk of CACS progression as compared to the reference group (HR: 1.653; 95% CI: 1.144-2.390), whereas MHO class II subjects did not (HR: 1.195; 95% CI: 0.514-2.778). Among subjects with MHO class I, no significant CACS progression was observed in the subjects who maintained metabolic health during follow-up (HR: 1.448; 95% CI: 0.921-2.278). CONCLUSIONS: The risks of metabolic deterioration and CACS progression were significant in subjects with MHO class I, but not in those with MHO class II.

Clinical whole exome sequencing in early onset diabetes patients.

AIMS: There could be an overlap of monogenic diabetes and early onset type 2 diabetes in those who are diagnosed before age of 30years. Genetic diagnosis in these patients might improve the quality of care. A limited number of studies have used whole exome sequencing (WES) in Asian patients with early onset diabetes, and the clinical utility of WES is largely unknown. METHODS: We performed whole exome capture and massive parallel sequencing in 28 patients with early onset diabetes. Those who had a strong family history of diabetes were preferentially enrolled. Rare and non-silent variants in 29 genes known to cause monogenic diabetes, including 12 maturity-onset diabetes of the young (MODY) genes, were investigated for pathogenicity. RESULTS: The average depth of on-target WES reads was 97 X. A total of four pathogenic or likely pathogenic rare missense variants (p.Leu319Pro in HNF4A, p.His103Tyr and p.Arg74Gln in ABCC8, and p.Leu139Val in HNF1A) in MODY genes were identified in three patients. Although four rare non-silent variants in MODY genes (p.Arg183Cys in PAX4, p.Val139Ile and p.Pro740fs in CEL, and p.Val147Ile in HNF4A) and two rare non-silent variants in monogenic diabetes genes (p.Glu169Lys in WFS1, and p.Pro407Gln in GATA4) were identified, their pathogenicity was uncertain or likely benign. CONCLUSIONS: WES could be an initial option for genetic testing in patients with early onset diabetes. However, sufficient and universal coverage of genes of interest is required. In addition, it could be difficult to interpret variant pathogenicity, and these cases might require further validation.

Clinical implications of various criteria for the biochemical diagnosis of insulinoma.

BACKGROUND: Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas. METHODS: We reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria. RESULTS: Fulfilling all three Endocrine Society criteria-plasma levels of glucose (<3.0 mmol/L), insulin (≥8 pmol/L), and C-peptide (≥0.2 nmol/L)-exhibited 100% sensitivity and 89% specificity. Fulfilling the glucose and C-peptide criteria showed 100% sensitivity and 83% specificity, while fulfilling the glucose and insulin criteria showed 100% sensitivity and 72% specificity. Among the ratio criteria, the insulin-glucose ratio [>24.0 (pmol/L)/(mmol/L)] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity. CONCLUSION: Fulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.

A novel mutation in the von hippel-lindau tumor suppressor gene identified in a patient presenting with gestational diabetes mellitus.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. To date, more than 1,000 germline and somatic mutations of the VHL gene have been reported. We present a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus. METHODS: A 30-year-old woman presented with gestational diabetes mellitus. She sequentially showed multiple pancreatic cysts, spinal cord hemangioblastoma, cerebellar hemangioblastoma, and clear cell type renal cell carcinomas. Also, her father and brother had brain hemangioblastomas. Each of the three exons of the VHL gene was individually amplified by polymerase chain reaction and direct sequencing was performed using an ABI 3730 DNA analyzer. RESULTS: DNA sequence analysis to determine the presence of VHL mutation in her family revealed del291C, a novel frameshift mutation. CONCLUSION: We found a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.