Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea

Background/Aims@#We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. @*Methods@#Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. @*Results@#The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. @*Conclusions@#The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Is an Oral Glucose Tolerance Test Still Valid for Diagnosing Diabetes Mellitus?

BACKGROUND: We evaluated the diagnostic rate of diabetes using fasting plasma glucose (FPG), 2-hour plasma glucose (2h PG) after 75 g oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels, and we elucidated the pathophysiologic characteristics and risk factors that give rise to diabetes in patients with prediabetes. METHODS: The data of 236 patients who had the OGTT at Konkuk University Hospital were analyzed. Fasting, 30, and 120 minutes blood glucose levels and insulin levels were measured. The diagnostic rate of diabetes was assessed using FPG, 2h PG, and HbA1c levels. The clinical data and insulin resistance and secretion evaluations were compared using indexes according to the fasting glucose level. RESULTS: Among 236 subjects, 97 (41.1%) were diabetics and 102 (43.2%) were prediabetics. The rate of diabetes diagnosis by one of the individual criteria was 56.7%, 53.6%, and 84.5% for FPG, HbA1c, and 2h PG, respectively. When two criteria were used to diagnose diabetes, 72.2% of the diabetic patients were identified by FPG and HbA1c, while 100% were identified by FPG and 2h PG, and 91.7% were identified by 2h PG and HbA1c. The HbA1c cut-off value for 2h PG ≥200 mg/dL was 6.1%, and the FPG cut-off value was 115 mg/dL. In impaired fasting glucose subjects, the HbA1c level, Matsuda index, and insulinogenic index were associated with risk of occurrence of overt diabetes (P<0.01). CONCLUSION: This study suggests that performing additional OGTT for patients with FPG ≥110 mg/dL or HbA1c ≥6.1% is helpful to reclassify their glucose tolerance status and evaluate their potential for progressing to overt diabetes.

The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults

BACKGROUND: The common characteristics of metabolic syndrome (MetS) and Cushing's syndrome suggest that excess cortisol may be involved in the pathogenesis of MetS. Salivary cortisol measurements are simple and can be surrogates for plasma free cortisol, which is the most biologically active form. We evaluated the association between levels of midnight salivary cortisol and MetS in Korean adults. METHODS: A total of 46 subjects, aged 20 to 70 years, who visited the Health Care Center at Konkuk University Hospital from August 2008 to August 2009 were enrolled. We compared the levels of midnight salivary cortisol in subjects with MetS with those in subjects without MetS. We analyzed the associations between midnight salivary cortisol levels and components of MetS. RESULTS: Midnight salivary cortisol levels were higher in the MetS group (70+/-42.4 ng/dL, n=12) than that in the group without MetS (48.1+/-36.8 ng/dL, n=34) (P=0.001). Positive correlations were observed between midnight salivary cortisol levels and waist circumference, fasting blood glucose, and homeostasis model assessment of insulin resistance. The risk for MetS was significantly higher in subjects with midnight salivary cortisol levels > or =100 ng/dL than in those with levels <50 ng/dL (odds ratio, 5.9; 95% confidence interval, 2.35 to 36.4). CONCLUSION: The results showed a positive correlation between midnight salivary cortisol levels and MetS, suggesting that hypercortisolism may be related to MetS.

Treatment Strategy for Diabetes with Cardiovascular Disease / 임상당뇨병

Individuals with diabetes mellitus are at 2- to 3-fold increased risk of cardiovascular disease relative to individuals without diabetes, and hypoglycemia is associated with increased cardiovascular mortality in diabetic patients. Here, we present a discussion of multiple hypoglycemic drugs and their cardiovascular effects. In addition, we provide summary recommendations for glucose-lowering regimens in patients with diabetes and cardiovascular diseases.

A Case of Type 2 Diabetes Mellitus Improved after Surgical Treatment of Primary Hyperparathyroidism / 임상당뇨병

Patients with primary hyperparathyroidism often exhibit insulin resistance and glucose intolerance. In previous studies, glucose intolerance was improved by parathyroidectomy in primary hyperparathyroidism. We report a case of type 2 diabetes mellitus that improved after resection of a parathyroid adenoma along with a review of the literature.

Hypoglycemia due to Focal Nesidioblastosis in a Patient with Type 2 Diabetes Mellitus / 당뇨병

We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.

Effects of lovastatin on free fatty acid oxidation in human skeletal muscle cells / 대한내과학회지

BACKGROUDN: Recent clinical studies have suggested that statins improve insulin resistance and glucose metabolism in the skeletal muscle of diabetic patients. To evaluate a possible component of this action, we measured free fatty acid oxidation in cultured human skeletal muscle cells (HSMC). METHODS: Seven normal controls and 7 type 2 diabetic patients underwent quadriceps muscle biopsy. The HSMCs (n=14) were treated with or without lovastatin (Lova, 20 micrometer) for 2 days, and the free fatty acid (FFA) oxidation was measured. RESULTS: Lova increased the oxidation of the long-chain FA palmitate to 271.2+/-32.7% of the control (p<0.01). Oxidation of the medium chain FA octanoate also increased after treatment of Lova (158.3+/-21.9%, p<0.05). One pathway of regulation of FFA is through AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation. Following Lova treatment, AMPK phosphorylation did not show a significant change while the total protein expression of AMPK was decreased (73.6+/-6.2% of the control, p<0.01). Lova treatment significantly increased ACC phosphorylation (149.5+/-20.6% of the control, p<0.05). CONCLUSION: Lova increased FFA oxidation by increasing the ACC phosphorylation in human skeletal muscle cells. Stimulation of skeletal muscle FFA oxidation may be one mechanism by which statins act to lower intramyocellular triglyceride and improve insulin action on glucose metabolism.

A case of necrotizing fasciitis caused by Klebsiella pneumoniae secondary to chronic otitis media / 대한내과학회지

Necrotizing fasciitis is a relatively uncommon infectious disorder where a bacterial organism penetrates the subcutaneous tissues and superficial fascia, ultimately causing necrosis of vast areas of soft tissue. Although invasive Streptococcus spp., most commonly group-A streptococci, is the most frequent cause of this disorder, in a single organism-infection, necrotizing fasciits caused by Klebseilla pneumoniae is becoming more frequently reported, perhaps due to the recent increase in the frequency of diabetes and liver diseases. Necrotizing fasciitis caused by K. pneumoniae is usually secondary to hematogenous dissemination, most commonly caused by trauma or liver abscess and usually results in multiple organ failure. The progression of the disease is so rapid that the mortality rate is high despite aggressive surgical intervention and extensive use of antibiotics at an early disease stage. Here we report a case of necrotizing fasciitis caused by hematogenously spread K. pneumoniae from incompletely treated chronic otitis media in a patient with alcoholic liver cirrhosis and diabetes.

The First Isolation of Chlamydia pneumoniae from a Korean Patient / 결핵

BACKGROUND: Chlamydia pneumoniae is one of common causes in upper and lower respiratory infections. Isolating C. pneumoniae from clinical specimens is very difficult due to the characteristics of the organism. Recently, we succeeded in isolating C. pneumoniae from a Korean patient, who suffered from acute pharyngitis. This is the first isolate from a clinical specimen in Korea. METHOD: We attained a nasopharyngeal swab from a 22-year-old female patient, and inoculated it on a monolayer of the Hep-2 cell line. After 8 passages, we found the inclusion bodies of C. pneumoniae by an immunofluorescence(IF) test. The species-specific monoclonal antibody IF staining and species-specific PCR were done to confirm the species of the isolate, and electron microscopy was used to characterize the morphology. RESULT: The isolate was confirmed to be C. pneumoniae by species-specific IF and PCR, and the strain was named LKK-1. The shape of the elementary body was round and with a narrow periplasmic space, as shown by electron microscopy, which is similar to the Japanese strain, but not the Western strain. CONCLUSION: We succeeded in isolating C. pneumoniae from a 22-year-old patient with acute pharyngitis, which is the first isolate in Korea. In the future, this Korean strain will be useful to the study of C. pneumoniae.

A Case of Insulin: dependent Diabetes Mellitus Carrying the 3243 bp tRNALUR(UUR)-- Point Mutation of Mitochondrial DNA / 대한내과학회지

We describe a case of insulin-dependent diabetes mellitus(lDDM) with a mutation at nucleotide 3243 of mitochondrial DNA. A 24-years-old female presented with recurrent episodes of generalised tonic clonic seizures, cognitive decline, short stature, bilateral sensory neural hearing loss, bilateral optic neuropathy, lactic acidosis, and basal ganglia calcifications in addition to IDDM. Maternal transmission of the disease was suggested, by the fact that her mother have died of diabetic complications of the age of 50. Heteroplasmy of wild type and mutant mitochondrial DNA derived from peripheral leucocytes was detected by Apa I digestion of the polymerase chain reaction products amplified with a set of primer for tBNALUR(UUR) Adenosin-to guanidine substitution, occurring at nucleotide position 3243 in tRNALUR(UUR) gene in comparison with reference sequences was confirmed.