Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes

Background@#This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes. @*Methods@#This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness. @*Results@#The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders. @*Conclusion@#HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene

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Serum Chemerin Levels are Associated with Visceral Adiposity, Independent of Waist Circumference, in Newly Diagnosed Type 2 Diabetic Subjects

PURPOSE: Chemerin has been suggested to be linked to insulin resistance and type 2 diabetes mellitus (T2DM). However, the relationship between visceral adiposity and chemerin levels remains unclear in subjects with T2DM. In this study, we investigated the relationship between serum chemerin levels and visceral adiposity. MATERIALS AND METHODS: This study included 102 subjects newly diagnosed with T2DM. The relationships between serum chemerin levels and clinical and biochemical parameters were examined. Multiple linear regression analysis was performed to determine the predictable factors of serum chemerin levels. RESULTS: Serum chemerin levels showed significant positive correlations with body mass index (BMI), waist circumference (WC), visceral fat thickness (VFT), insulin levels, the homeostasis model assessment of insulin resistance, and levels of triglycerides (log-transformed) and high-sensitivity C-reactive protein, while showing significant negative correlations with high-density lipoprotein cholesterol. After adjusting for BMI and WC, VFT showed a significant relationship with serum chemerin levels (r=0.222, p=0.027). Moreover, VFT was an independent predictive factor of serum chemerin levels (β=0.242, p=0.041). CONCLUSION: We demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM.

Hypopituitarism Secondary to Paraclinoid Internal Carotid Artery Aneurysm / 대한내과학회지

Pituitary insufficiency due to a sellar aneurysm is relatively uncommon. The prevalence of this disorder was <0.2% in a large cohort of patients with panhypopituitarism. While uncommon, a vascular sellar lesion should be included as a differential diagnosis for a sellar mass resulting in hypopituitarism. We report herein a case of hypopituitarism with hyperprolactinemia secondary to a large (1.7-cm) saccular aneurysm at the left paraclinoid internal carotid artery.

A Potential Issue with Screening Prediabetes or Diabetes Using Serum Glucose: A Delay in Diagnosis

The aim of this study was to compare the fasting serum glucose level with the fasting plasma glucose level for diagnosing hyperglycemic states in real-life clinical situations. Additionally, we investigated a usual delay in sample processing and how such delays can impact the diagnosis of hyperglycemic states. Among 1,254 participants who had normoglycemia or impaired fasting glucose (IFG) assessed by the fasting serum glucose level, 20.9% were newly diagnosed with diabetes based on the plasma fasting glucose level. Of the participants with normoglycemia, 62.1% and 14.2% were newly diagnosed with IFG and diabetes, respectively, according to the plasma fasting glucose level. In our clinical laboratory for performing health examinations, the time delay from blood sampling to glycemic testing averaged 78±52 minutes. These findings show that the ordinary time delay for sample processing of the serum glucose for screening hyperglycemic states may be an important reason for these diagnoses to be underestimated in Korea.

Glycosylated Hemoglobin Threshold for Predicting Diabetes and Prediabetes from the Fifth Korea National Health and Nutrition Examination Survey

We aimed to estimate the threshold level of glycosylated hemoglobin (HbA1c) for the fasting plasma glucose of 100 and 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 4,481 participants over 19 years of age without diabetic medications and conditions to influence the interpretation of HbA1c levels, such as anemia, renal insufficiency, liver cirrhosis, and cancers, were analyzed. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal HbA1c cutoff value. A HbA1c threshold of 6.35% was optimal for predicting diabetes with a sensitivity of 86.9% and a specificity of 99.1%. Furthermore, the threshold of HbA1c was 5.65% for prediabetes, with a sensitivity of 69.3% and a specificity of 71%. Further prospective studies are needed to evaluate the HbA1c cutoff point for diagnosing prediabetes and diabetes in the Korean population.

Effects of the Serum Adiponectin to Tumor Necrosis Factor-alpha (TNF-alpha) Ratio on Carotid Intima-Media Thickness in Newly Diagnosed Type 2 Diabetic Patients

OBJECTIVES: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor - alpha (TNF-alpha), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-alpha ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-alpha levels on the progression of carotid atherosclerosis. METHODS: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-alpha were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-alpha levels (ADPN/TNF-alpha), baseline CIMT, and progression of CIMT at 1 year. RESULTS: ADPN/TNF-alpha negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011+/-0.138 mm). There was a negative correlation between ADPN/TNF-alpha and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. CONCLUSION: ADPN/TNF-alpha was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

Impact of Serum Adiponectin Concentration on Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Increased cardiovascular events, which is the leading cause of death in type 2 diabetic patients, are mainly caused by accelerated atherosclerosis. Adiponectin has been suggested as a risk factor for cardiovascular diseases in cross-sectional studies. However, little is known about the impact of adiponectin on the progression of carotid atherosclerosis in type 2 diabetic patients. This study was conducted to evaluate the impact of early adiponectin levels on the progression of carotid atherosclerosis. METHODS: From March 2009, 150 patients with type 2 diabetes were consecutively enrolled in our affiliated outpatient clinic. Anthropometric and biochemical data, including adiponectin levels, were measured in each participant. We measured the carotid intima-media thickness (CIMT) at baseline and at 1-year follow-up (n = 111). Then, we prospectively studied the relationship between the serum adiponectin levels and the progression of CIMT for 1 year. RESULTS: Adiponectin levels negatively correlated with CIMT (r = -0.219, P = 0.015). Moreover, mean progression of CIMT was 0.016 +/- 0.040 mm. However, there was no correlation between adiponectin levels and the progression of CIMT within 1-year follow-up period (r = -0.156, P = 0.080). Age (beta = 0.556, P = 0.004), LDL cholesterol (beta = 0.276, P = 0.042), and A1C (beta = 0.309, P = 0.038) were found to be independent risk factors for CIMT. However, A1C (beta = 0.311, P = 0.042) was found to be the only independent risk factor for the progression of CIMT. CONCLUSION: In our study, adiponectin levels were negatively associated with CIMT. However, it did not affect the progression of CIMT at 1-year follow-up. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

A Case of Familial Hypocalciuric Hypercalcemia Coexisting with Hypothyroidism / 대한내과학회지

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder characterized by mild asymptomatic hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, and normal or elevated parathyroid hormone levels. FHH is caused by an inactivating heterozygous mutation of the calcium-sensing receptor (CaSR) gene. A 62-year-old woman was referred to our center because of inadequate glucose control. Her son had hypercalcemia. Biochemical and endocrine studies showed hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, normal parathyroid hormone levels, normal PTH-related peptide levels, decreased free T4, increased TSH, and thyroid antibody positivity. Direct sequencing analyses revealed a heterozygous mutation of G21R at exon 2 and a single nucleotide polymorphism of R990G at exon 7 of the CaSR gene. Here, we report a case of FHH associated with a heterozygous mutation and a single nucleotide polymorphism of the CaSR gene, which coexisted with autoimmune thyroiditis and hypothyroidism. To our knowledge, this is the first such case reported.

Case of Thyroid Hormone Resistance Syndrome with a Mutation in the Thyroid Hormone Receptor Beta Gene / 대한내과학회지

In thyroid hormone resistance syndrome (THR) TSH levels are normal or elevated despite thyroid hormone levels being elevated. THR is distinguished from TSH-producing pituitary adenoma by TRH stimulation and alpha-subunit tests, thyroid hormone receptor (TR) beta gene analysis, and sellar MRI. A 24-year old man with diffuse goiter visited our hospital complaining of fatigue, heat intolerance, palpitation, and weight loss. He had elevated total T3 and free T4 levels, but normal TSH levels. Serum TSH levels during TRH stimulation tests performed before and after T3 suppression showed normal and non-suppressible responses, respectively. The serum basal alpha-subunit test result was normal. A TR beta gene R438H mutation was identified, and a pituitary mass with cystic change was identified by sellar MRI. We report a case of THR with a mutation (R438H) in the TR beta gene, the first case of its kind in Korea.

A case of hyperglycemia-induced hemiballism-hemichorea associated with diabetic ketoacidosis / 대한내과학회지

Hemiballism-hemichorea (HB-HC) is defined as continuous, non-patterned, and involuntary movement involving one side of the body and is often associated with endocrine diseases such as diabetes mellitus (DM) and hyperthyroidism. In Korea, 16 cases of HB-HC associated with non-ketotic hyperglycemia have been reported. Here, we report the first known case of HB-HC associated with type 2 DM and diabetic ketoacidosis (DKA). A 32-year-old man visited our hospital complaining of hemichoreoballistic movement. The patient had no history of DM. In a neurological examination and laboratory tests, HB-HC associated with type 2 DM and DKA was diagnosed. The patient was immediately treated with intravenous hydration and insulin therapy, and completely recovered. DKA and non-ketotic hyperglycemia should be considered as a possible cause of HB-HC, although these are very rare. In HB-HC associated with DKA, strict blood glucose control is needed.

Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients? / 당뇨병

BACKGROUND: Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated. RESULTS: With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093). CONCLUSION: Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

A case of hyperosmolar nonketotic coma associated with androgen deprivation therapy in prostate cancer / 대한내과학회지

During advanced prostate cancer, androgen deprivation therapy (ADT) using gonadotropin-releasing hormone and antiandrogen is an effective treatment modality. Recently, it has been reported that ADT may result in diabetes mellitus (DM), metabolic syndrome, and cardiovascular disease. Here, we report the first case in the literature of new-onset DM and hyperosmolar nonketotic coma (HNKC) associated with ADT. A 69-year-old man visited our hospital because of altered mentality. The patient had been taking leuprolide and bicalutamide for metastatic prostate cancer for the past 4 months. In laboratory tests, new-onset DM with HNKC was diagnosed. The patient was immediately treated with intravenous hydration and insulin therapy, and recovered without sequela. Because ADT can cause DM, or rarely HNKC, it is necessary to monitor fasting blood glucose and lipid profiles carefully while ADT is performed.

Effect of Valsartan on Blood Pressure and Urinary Albumin Excretion in Hypertensive Type 2 Diabetic Patients: An Open-Label, Multicenter Study / 당뇨병

BACKGROUND: Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. METHOD: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. RESULT: Baseline mean systolic and diastolic blood pressure was 143 +/- 15 and 87 +/- 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction in systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to normoalbuminuria and twelve (41%) patients with macroalbuminuria improved to microalbuminuria. We found an association between the improvement of blood pressure and UAER (R = 0.165, P = 0.015). CONCLUSION: We concluded that valsartan reduces urinary albumin excretion and blood pressure in hypertensive type 2 diabetic patients.

The relationship between osteoprotegerin gene polymorphism and aortic calcification in Korean women / 대한내과학회지

BACKGROUND: Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-kappa B ligand (RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. Recently, OPG has been proposed as a link molecule between osteoporosis and arterial calcification, but the relationship between OPG gene and cardiovascular system in human populations is unclear. Thus, the aim of this study was to investigate the relationship between OPG gene polymorphisms and aortic calcification in healthy Korean women. METHODS: We observed 251 healthy Korean women (mean age, 51.3+/-6.9 yr). We determined cardiovascular risk factors. Thoracic and abdominal aortic calcifications were examined by simple radiological methods. A163G, G209A, T245G, and T950C polymorphisms of OPG gene were analyzed by allelic discrimination using the 5' nuclease polymerase chain reaction assay. RESULTS: The frequency of mutant allele was increased in the aortic calcification (+) group as compared with aortic calcification (-) group (G209A, 28.6% vs. 18.7%, p=0.029; T950C, 75.9% vs. 65.4%, p=0.017). However, no significant relationship was found between OPG gene polymorphisms and serum OPG levels and cardiovascular risk factors. CONCLUSIONS: We observed that the OPG gene polymorphisms were partly associated with aortic calcification in healthy Korean women. Further studies are needed to clarify this relationship.

The relationship of adiponectin, leptin and ghrelin to insulin resistance and cardiovascular risk factors in human obesity / 대한내과학회지

BACKGROUND: Adiponectin, letin and ghrelin are considered to take part in the regulation of energy metabolism. We investigated the relationship between these adipokines and body mass index (BMI), regional adiposity, insulin resistance and cardiovascular risk factors in human. METHODS: Eighty six (Male : Female = 36 : 50, Age = 21-71 year old, BMI : 18 - 39.5 kg/m2) subjects without known medical problems participated in this study. Subjects were grouped based on BMI or visceral fat area (VFA) and gender. We measured lipid concentration, fasting glucose, fasting insulin, insulin resistance (HOMA-IR) and high sensitivity CRP (hsCRP). Body fat distribution was determined by computed tomography. Fasting serum adiponectin, leptin, and ghrelin were measured by ELISA. RESULTS: The group of BMI over 25 kg/m2 showed significant difference in waist circumference (WC), total fat area (TFA), subcutaneous fat area (SFA), VFA, Triglyceride (TG), hsCRP and leptin. Visceral fat dominant (VFD) group (VFA>or=100 cm2 or VFA/SFA>or=0.4) showed significant difference in age, BMI, WC, TFA, SFA, free fatty acid, HOMA-IR, hsCRP, adiponectin, leptin and ghrelin. Leptin was positively correlated with BMI, waist hip ratio (WHR), TFA, VFA, SFA, low-density lipoprotein cholesterol (LDL-C), HOMA-IR and fasting insulin. Adiponectin was negatively correlated with BMI, WHR, TFA, VFA, HOMA-IR and positively correlated with High-density lipoprotein cholesterol (HDL-C). Ghrelin level was negatively correlated with WHR, VFA, fasting glucose, HOMA-IR and positively correlated with HDL-C. And leptin was negatively correlated with ghrelin. As regional adiposity, SFA was positively correlated with leptin, and VFA was negatively correlated with adiponectin and ghrelin and positively correlated with leptin. CONCLUSIONS: This study demonstrated that VFA had more significant association with lipid metabolism and adipokine secretion than BMI and leptin levels were inversely correlated with ghrelin level.

Duration of Preparation for Postoperative Radioiodine Administration in Differentiated Thyroid Carcinoma / 대한내분비학회지

BACKGROUND: Radioiodine treatment is effective for the removal of remnant thyroid tissues after thyroidectomy in patients with differentiated thyroid carcinoma. To induce the elevation of serum TSH level which facilitates the uptake of radioiodine into remnants, a 4 to 6 week interval between thyroidectomy and radioiodine administration has been established. During the period of preparation, most patients have experienced overt symptoms of hypothyroidism which have led to the development of alternative strategies. Some reports have suggested that the interval could be reduced to about 3 weeks with less symptoms. We reevaluated the adequate time needed for the elevation of serum TSH level above 30microU/mL after thyroidectomy. METHODS: Forty five patients who had undergone total thyroidectomy for differentiated thyroid carcinoma were investigated. Serum TSH and free T4 levels were measured one or more times within 3 weeks after operation(total 97 blood samples). Eighty nine blood samples were obtained within 15 days. RESULTS: In 41 patients (91.1%) serum TSH levels increased to 30 microU/mL until 15 days after operation. Until postoperative 21 days, serum TSH levels in all the other patients reached 30microU/mL. In linear equation, the daily increment of serum TSH levels was 2.62microU/mL for the first 8 days after operation and 5.34micorU/mL for the next 7 days. The half-life of serum free T4 levels showed marked individual variations. CONCLUSION: Measurement of serum TSH level at about 15 days after total thyroidectomy for differentiated thyroid carcinoma may be useful in determining the time of radioiodine administration.

The Relationship between the G395A Polymorphism in Promoter of the KLOTHO Gene with Cardiovascular Risk Factors and Bone Mineral Metabolism in Korean Women

BACKGROUND: A novel gene, termed klotho, has been identified as a suppressor of several aging phenotypes, a genetic defect in klotho in mice resulted in a syndrome resembling human aging, i.e., arteriosclerosis and osteoporosis, but the relationship between KLOTHO gene with cardiovascular system and bone metabolism in human populations is unclear. Thus, the aim of this study was to investigate the relationship between the KLOTHO polymorphism with cardiovascular risk factors and bone metabolism in Korean women. METHODS: In 243 women(mean age, 51.2+/-6.9 yr), cardiovascular risk factors and bone turnover markers were measured using standard methods. Bone mineral densities(BMD) were measured by dual energy X-ray absorptiometry. The genotyping of the KLOTHO G395A polymorphism were performed by allelic discrimination using a 5' nuclease polymerase chain reaction assay. RESULTS: Allele frequencies were 0.829 for the G allele and 0.171 for the A allele, which was in Hardy-Weinberg equilibrium. Mean systolic blood pressure(BP) was significantly higher in A allele carriers compared with non-carriers. In logistic regression analysis with the cardiovascular risk factors as the independent variable, only systolic BP was identified as a significant variable for A allele carriers. Mean lumbar spine BMD was significantly lower in A allele carriers compared with non-carriers. This difference became marginally significant after adjustment for age and BMI. CONCLUSION: We observed that the KLOTHO G395 polymorphism is related with BP in Korean women. Also, these data suggest that the KLOTHO G395 polymorphism was marginally associated with lumbar spine BMD in Korean women.