Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea

BACKGROUND: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia. RESULTS: The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011). CONCLUSION: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Expression and Regulation of Osteoprotegerin in Adipose Tissue

PURPOSE: Osteoprotegerin (OPG), a potent inhibitor of osteoclastic bone resorption, has a variety of biological functions that include anti-inflammatory effects. Adipocytes and osteoblasts share a common origin, and the formation of new blood vessels often precedes adipogenesis in developing adipose tissue microvasculature. We examined whether OPG is secreted from adipocytes, therefore contributing to the prevention of neovascularization and protecting the vessels from intimal inflammation and medial calcification. MATERIALS AND METHODS: The mRNA expression of OPG and receptor activator of NF-kappaB ligand (RANKL) was measured in differentiated 3T3L1 adipocytes and adipose tissues. RESULTS: OPG mRNA expression increased with the differentiation of 3T3L1 adipocytes, while RANKL expression was not significantly altered. OPG mRNA was expressed at higher levels in white adipose tissue than in brown adipose tissue and was most abundant in the epididymal portion. In differentiated 3T3L1 adipocytes, Rosiglitazone and insulin reduced the OPG/RANKL expression ratio in a dose- and time- dependent manner. In contrast, tumor necrosis factor-alpha (TNF-alpha) increased the expression of both OPG and RANKL in a time-dependent manner. The OPG/RANKL ratio was at a maximum two hours after TNF-alpha treatment and then returned to control levels. Furthermore, OPG was abundantly secreted into the media after transfection of OPG cDNA with Phi C31 integrase into 3T3L1 cells. CONCLUSION: Our results indicate that OPG mRNA is expressed and regulated in the adipose tissue. Considering the role of OPG in obesity-associated inflammatory changes in adipose tissue and vessels, we speculate that OPG may have both a protective function against inflammation and anti-angiogenic effects on adipose tissue.

Characteristics of Type 2 Diabetes in Terms of Insulin Resistance in Korea

The aim of this study was to assess the implications of insulin resistance on the clinical and biochemical profiles of Korean type 2 diabetic patients. 122 patients with type 2 diabetes underwent a short insulin tolerance test to assess insulin resistance. Subjects were classified in tertiles according to ISI (insulin sensitivity index), and the tertile I (the insulin- resistant group) and tertile III (the insulin-sensitive group) clinical and biochemical parameters were compared. Age, waist circumference (WC), systolic blood pressure (SBP), HbA1c, body fat content, and fasting plasma glucose were significantly higher in tertile I than tertile III (all p < 0.05). The frequency of hypertension and family history of cerebrovascular disease (CVD) were greater in tertile I than III (p < 0.05). To evaluate the factors affecting ISI, multiple regression was performed, and age, WC, SBP, HbA1c, and body fat content were found to be independently related to insulin resistance (p < 0.05). Old age, hypertension, central obesity, and poor glycemic control were identified as clinical parameters of insulin resistance in Korean type 2 diabetic patients.

Apolipoprotein E and ACE genetic polymorphism and nephropathy in type 2 diabetic patients / 대한내과학회지

BACKGROUND: The aim of this study was to investigate the association between apo E and ACE genetic polymorphism and diabetic nephropathy. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (E2, E3, E4) and three ACE groups (II, ID, DD). Plasma levels of lipids were measured. The frequency of diabetic nephropathy and clinical and biochemical characteristics were compared among the Apo E and ACE genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (46.7%) than apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that odds ratio of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (p<0.01) and 0.643 (p=0.583), respectively. Plasma TG levels were significantly greater in apo E2 patients. This study did not show an association between ACE gene polymorphism and diabetic nephropathy, and no interaction between Apo E and ACE gene polymorphism. CONCLUSION: Apo E2 is a prognostic risk factor for diabetic nephropathy in Korean type 2 diabetes. TG may have an important role of diabetic nephropathy. There were not synergistic effect between Apo E and ACE gene polymorphism in diabetic nephropathy.

The Correlation between Insulin Resistance and the Visceral Fat to Skeletal Muscle Ratio in Middle-aged Women

Central obesity with visceral fat accumulation and the amount of skeletal muscle mass may influence insulin sensitivity via its capacity for glucose load uptake. We investigated the relationships among the following metabolic variables: ratio of fat area to skeletal muscle area (VMR), percent ideal body weight, body mass index, waist-to-hip circumference (WHR) and visceral fat to subcutaneous fat ratio (VSR) in 114 nondiabetic middle-aged women. Anthropometric parameters, lipid profiles and sex hormone- binding globulin were measured. Visceral and subcutaneous fat areas at the umbilical level and the skeletal muscle area at the mid-thigh level were measured and computed. 75-gram OGTT tests were performed, along with measuring plasma glucose, insulin and free fatty acid levels, according to which area under the curve of glucose (Glu-AUC), insulin (Ins-AUC), free fatty acid (FFA-AUC) and glucose/insulin ratio (GIR=Glu- AUC/Ins-AUC), were calculated. 1) Triglyceride was more correlated with VSR than VMR. 2) The independent anthropometric parameters for each metabolic variable were In conclusion, VMR for Ins-AUC, WHR for Glu-AUC and total cholesterol, and VSR for triglyceride. 3) For subjects with higher VMR, age, Ins-AUC and triglyceride were significantly higher. 4) Subjects with higher VMR were older and showed higher Ins-AUC and lower GIR than the subjects with lower VMR. In conclusion, VMR is an anthropometric parameter that reflects insulin resistance concerning glucose metabolism, and VSR is thought to be a good parameter that that reflects the serum lipid levels. Further prospective studies are necessary to reevaluate the visceral fat vs. skeletal muscle relationship.

Definition and Epidemiology of Obesity

Obesity can be defined as the excessive accumulation of fat in adipose tissues, to the extent that health may be impaired. The most widely used measures of total and abdominal adiposity are the body mass index (BMI) and waist circumference, respectively. During the past several decades, the prevalence of obesity has increased substantially, making it a true epidemic and a public health crisis, with about 315 million people worldwide estimated to fall into the WHOdefined obesity categories with BMI of 30 or above. Indeed, the obesity epidemic has been already leading to dramatic increases in type 2 diabetes and metabolic syndromes. On the other hand, there are substantial risks for morbidity in obese children even before they reach adulthood, and if obesity in childhood persists into the adult years, the morbidity and mortality are greater than if the obesity developed in adulthood. The major causes of the rapid global rise in obesity rates lie in the profound environmental and societal changes now affecting large parts of the world and creating societies in which physical activities are low and the availability of highfat, energydense foods has increased. Strategies aimed at preventing weight gain and obesity are likely to be more cost effective and to have a greater positive impact on the longterm control of body weight than treating obesity once it has developed.

A Case of Hepatomegaly due to Diabetic Glycogenosis Reversed by Glycemic Control / 대한내분비학회지

Diabetes mellitus is well known to be associated with various structural and functional liver abnormalities. If diabetic patients are accompanied by hepatomegaly or abnormal findings from a liver function test, the most common pathological findings are steatosis and glycogenosis. The steatosis is characterized by deposition of macrovesicular fat droplets in the hepatocytes, which is common in obese, type 2 diabetes mellitus. If macrovesicular steatosis is combined with mixed inflammatory infiltrate, without evidence of alcoholic hepatitis, the case could be diagnosed as nonalcoholic steatohepatitis (NASH). NASH has the possibility of progressing to cirrhosis. Secondary glycogenosis is common in uncontrolled type 1 diabetes mellitus, and is completely reversible. A 22-year-old male, with uncontrolled type 1 diabetes mellitus, was admitted with anorexia, nausea and right upper quadrant pain. Hepatomegaly and elevated aminotransferases were noted. He was diagnosed as diabetic glycogenosis using computed tomogram and liver biopsy. The hepato megaly and liver function test abnormalities were markedly improved with glycemic control

Graves' Disease Associated with Klinefelter's Syndrome

Klinefelter's syndrome is one of the most common forms of primary hypogonadism and infertility in males. It is characterized by small and firm testes, gynecomastia, azoospermia, and an elevated gonadotropin level. The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome. We report upon a 35 year-old male patient with Graves' disease in association with Klinefelter's syndrome; as confirmed by chromosome analysis. The patient is being treated with antithyroid medication for Graves' disease and by testosterone replacement for Klinefelter's syndrome.

The Effect of Iodine Restriction on Thyroid Function in Patients with Hypothyroidism Due to Hashimoto's Thyroiditis

Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 microgram/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 microIU/mL at the baseline, 25.66 +/- 70.79 microIU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 microIU/mL vs. 123.14 +/- 156.51 microIU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.

A Case of Riedel's Thyroiditis in a Patient with a History of Subacute Thyroiditis / 대한내분비학회지

Riedel's thyroiditis is a rare form of chronic thyroiditis, characterized by a fibroinflammatory process which partially destroys the thyroid, often involving surrounding tissues. The relationship of Riedel's thyroiditis to other forms of thyroiditis is not clear. A case of Riedel's thyroiditis in a 51-year-old female patient, admitted with a previous diagnosis of subacute thyroiditis, is reported. She was first diagnosed with subacute thyroiditis based on clinical manifestation and radiologic and laboratory results. She was treated with glucocorticoid for 8 weeks. The follow-up lasted for 12 months. However, three years later she underwent a thyroidectomy operation due to an enlargement of the thyroid nodule and suspicion of malignancy. Histopathologic examination confirmed that she had Riedel's Thyroiditis. Until now, few case of Riedel's thyroiditis in patients with a history of subacute thyroiditis have been reported in the literature. Although the etiology of Riedel's thyroiditis is unknown, it may develop in the course of subacute thyroiditis.

A Case of Thyroid Storm Due to Thyrotoxicosis Factitia

We describe a case of thyroid storm due to thyrotoxicosis factitia, which was caused by the ingestion of excessive quantities of exogenous thyroid hormone for the purpose of reducing weight. An 18-year-old female was admitted to the hospital 24 hours after taking up to 50 tablets of synthyroid (1 tablet of synthyroid : levothyroxine 100 microgram). Because of her stuporous mental state and acute respiratory failure, she was intubated and treated in the intensive care unit. After reviewing her history carefully and examining plasma thyroid hormone levels, we diagnosed this case as a thyroid storm due to thyrotoxicosis factitia. Her thyroid function test revealed that T3 was 305 ng/dL, T4 was 24.9 microgram/dl, FT4 was 7.7 ng/dL, TSH was 0.05 micro IU/mL and TBG was 12.84 microgram/mL (normal range: 11.3 - 28.9). TSH receptor antibody, antimicrosomal antibody, and antithyroglobulin antibody were negative. She was recovered by treatment, namely, steroid and propranolol, and was discharged 8 days after admission. Thyroid storm due to thyrotoxicosis factitia caused by the ingestion of excessive thyroid hormone is rarely reported worldwide. Therefore, we now report a case of thyroid storm that resulted from thyrotoxicosis factitia caused by the ingestion of a massive amount of thyroid hormone over a period of 6 months.

A Case of Endophthalmitis due to Group G beta-hemolytic Streptococcus Sepsis / 감염과화학요법

Identified first by Lancefield and Hare in 1935, the group G streptococcus occurs as commensals in the skin, pharynx, intestine, and vagina. It has been reported to cause a variety of human infections, such as sepsis, endocarditis, peritonitis, pharyngitis, and infective arthritis. Group G streptococcus sepsis could occur in chronic states such as malignancy, diabetes, alcoholics, neurologic disease, cardiovarscular disease, and end stage renal disease, however, there has been only a few case reports of endogenous endopthalmitis caused by group G streptococcus. We report herein endogenous endopthalmitis caused by group G streptococcus sepsis in 64-year-old man of alcoholic.

A Case of Endophthalmitis due to Group G beta-hemolytic Streptococcus Sepsis / 감염과화학요법

Identified first by Lancefield and Hare in 1935, the group G streptococcus occurs as commensals in the skin, pharynx, intestine, and vagina. It has been reported to cause a variety of human infections, such as sepsis, endocarditis, peritonitis, pharyngitis, and infective arthritis. Group G streptococcus sepsis could occur in chronic states such as malignancy, diabetes, alcoholics, neurologic disease, cardiovarscular disease, and end stage renal disease, however, there has been only a few case reports of endogenous endopthalmitis caused by group G streptococcus. We report herein endogenous endopthalmitis caused by group G streptococcus sepsis in 64-year-old man of alcoholic.